- Email: [email protected]
INFLUENCE OF HYPERBARIC OXYGEN ON THE SURVIVAL OF SPLIT SKIN GRAFTS
868
purging with large amounts of magnesium sulphate, both potent cholecystagogues, strongly suggests that V. cholerce may be harboured in the gallbladder during convalescence. In studies with the canine cholera model system Dr. R. B. Sack (personal communication) has had a single dog which continued to excrete vibrio intermittently in his stool without purge for 120 days during convalescence. At open surgery on the 56th day, the gallbladder was cultured by aspiration and 1000 vibrios per ml. were grown from the bile. Case 1 demonstrated all rough vibrios on the last three positive vibrio cultures. This corroborates a clinical impression that shortly before a patient becomes vibriofree the organism occasionally changes its morphological or antigenic character. It is generally believed that the vibrio is a rough non-pathogenic one. We are continuing to examine the patient in case 1 whose stools continued to yield vibrios, after purging, for at least 174 days. He last excreted vibrios which produced only smooth colonies on the 44th day after his last clinical symptom of cholera. The relative efficacy of the various antibiotic regimens used will be reported elsewhere. It is perhaps significant that the two positive patients were in the control group and received no antibiotics. We elected not to treat them subsequently to establish the duration of vibrioculture positivity. The value of antibiotics in preventing the convalescent carrier state or in treating carriers has not been determined. MacKenzie (1965) and Tamayo et al. (1965) have reported a very high incidence of symptom-free carriers in the recent cholera pandemic due to biotype El Tor. Mukerjee et al. (1965), among others, believe that V. cholerœ biotupe El Tor behaves differently from the classical vibrio, and considered it to be responsible for a different epidemiological pattern than that seen in previous cholera pandemics. Our findings do not confirm nor refute these opinions, but they do indicate that an inapparent carrier state may be present in the convalescent patient infected with V. cholerœ biotype El Tor. We thank Dr. R. N. Chaudhuri (former director) and Dr. J. B. Chatterjee, director, of the Calcutta School of Tropical Medicine, and their staffs; Dr. P. M. Manji, superintendent, and Prof. A. Das, clinical director, of the Infectious Diseases Hospital, and their staffs, for continued interest, advice and support of this study; and Dr. J. L. Boyer who was especially helpful in initiating this work. This work was supported in part by U.S. Public Health Service research grant no. H26. 6114 and in part by finding under Public to
gallbladder which emptied satisfactorily after cholecystokinin. In case 2, the gallbladder was not visualised even after a double dose of iopanoic acid (’ Telepaque ’). normal
INFLUENCE OF HYPERBARIC OXYGEN ON THE SURVIVAL OF SPLIT SKIN GRAFTS D. RESEARCH
J. D. PERRINS
M.B. Cantab., F.R.C.S. REGISTRAR, BURNS UNIT, QUEEN MARY’S HOSPITAL, ROEHAMPTON, LONDON S.W.15*
The possibility of obtaining increased survival of split skin grafts by the use of hyperbaric oxygen was investigated in a controlled clinical trial. This showed that a significant improvement can be obtained. In this series an increase in survival of 29% of the surface area of the grafts was achieved. A high proportion of complete " takes occurred; 64% of the treated cases as opposed to 17% of the controls. The results suggest that the method is valuable when extensive raw areas have to be covered, or when good cosmetic results are important. Summary
"
Introduction
of the fate of split skin grafts is not only of academic interest. Jackson (1961) stated that " the problem of successful closure of wounds with free split skin grafts is one of the important practical issues of wound " healing today. At present the average permanent " take of skin grafts on large open wounds, whether excised or granulating, is about 75%. This is clearly no ground for satisfaction and calls for improved technique and further basic research." In the patient with extensive burns it is important to obtain skin cover if life is to be saved, while the shortage of donor sites makes the survival of available skin doubly important. A
STUDY
Natural History of Skin Grafts The blood-vessels of a skin graft, after its removal from the donor site, are in a state of collapse and contain no red blood-
Law
480, section 104 (c), agreement no. 5x4317. Requests for reprints should be addressed to C.
K. W.
REFERENCES
Cole, J., Greenough, III, W. B. (1965) Lancet, ii, 972. Gangarosa, E. J., Saghari, H., Emile, J., Siadat, H. (1966) Bull. Wld Hlth Org. 34, 363. Greig, E. D. W. (1914) Indian J. med. Res. 2, 28. Kulesha, G. S., (1911) Patologicheskoi Anatomii Aziatskoi Kholery. St. Petersburg. MacKenzie, D. J. M. (1965) Publ. Hlth Serv. Publs, Wash. no. 1328, p. 341. Mukerjee, S., Basu, S., Bhattacharga, P. (1965) Br. med. J. ii, 837. Nikonov, A. G. (1958) J. Microbiol. Epidem. Immunol. 29, 40. Pollitzer, R. (1959) Monogr. Ser. W.H.O. no. 43. Rogers, L. (1952) Tropical Medicine (edited by L. Rogers and D. J. W. Megaw); p. 273. Simmonds, M. (1892) Dt. med. Wschr. 18, 931. Tamayo, J. F., Mosley, W. H., Alvero, M. G., Joseph, P. R., Gomez, C. Z., Montague, T., Dizon, J. J., Henderson, D. A. (1956) Bull. Wld Hlth Org. 33, 645. Valk, W. (1915) Geneesk. I. Ned.-Ind. 55, 561. Wallace, C. K., Carpenter, C. C. J., Mitra, P. P., Sack, R. B., Khanra, S. K., Werner, A. S., Duffy, T. P., Oleinick, A., Lewis, G. W. (1965) Trans. R. Soc. Trop. Med. Hyg. 59, 621.
Addendum
performed on Feb. 20, 1967. In normal visualisation of an apparently
Cholecystography case
1, there
was
was
1-Model of healing process of split skin grafts showing phases regression and recovery of enzyme activity (succinic dehydrogenase). (Wolff and Schellander 1965.)
Fig.
of
but recover at about 24 hours. They then dilate and contain fibrinogen-free fluid which quickly passes out into the substance of the graft to meet the metabolic requirements for several days. During this period of ischamua there is a low oxygen tension in the cells of the graft which is responsible for depression of mitotic activity (Dempster 1956). At about 48 hours vascular connection between the graft and its bed begins and is followed by fibroblastic invasion. By the fifth day the graft is well vascularised, mitotic activity returns as the result of the correction of hypoxia and is associated with hypertrophy and thickening of the epidermis, which continues
cells,
*
Present address: Institute of Orthopædics, Hospital, Stanmore, Middlesex.
Royal National Orthopiced
869
activity. The arrow indicates level at which the operation was performed. The first 4 days are characterised by a decline of enzyme activity, starting at the dermoepidermal junction and progressing to the deeper portion of the graft; the critical point occurring by the fourth day, when revascularisation starts and enzyme activity progresses to the dermoepidermal junction. Factors Influencing the Success of Split Skin Grafting The successful " take " of a split skin graft is finally dependent on its vascularisation from the underlying bed, and any factor impeding this ingrowth will mitigate against success. Clinical experience has shown that the following factors are important. Age.-The older the patient the more likelihood of a sclerotic blood-supply to the part. Anœmia.—The oxygen-carrying capacity of the blood must be
adequate to sustain the graft. The character of the recipient site.-A healthy viable base is required with no necrotic tissue, exposed tendon, or bone.
PROPORTION OF TREATED AND CONTROL CASES IN RELATION TO GRAFT SURVIVAL
Fig. 2-Survival of split skin grafts
in treated and control groups.
increase until the sixteenth day, when a peak is reached in capillary invasion and cellular hyperplasia (Conway et al. 1951, Sevitt 1957). Elegant enzyme-histochemical studies have revealed a striking decline in enzyme activity in split skin grafts during the first postoperative days (Wolff and Schellander 1965). If enzyme activity is a measure of oxidative metabolism, such studies reflect the degree and progression of hypoxia in the graft. Fig. 1 shows Wolff and Schellander’s (1965) model. The segments represent normal skin and specimens taken on the lst to the 20th postoperative day. Shades of grey and black indicate intensity and distribution of succinic-dehydrogenase
to
Overall improvement 29 % (mean value of permanent graft survival of 91’7% in treated group less 62’7% in the controls).
Fresh granulations’ provide better vascularisation than those that have been present for some time. Infection.-Group A &bgr;-hæmolytic streptococci and Pseudomonas pyocynea in particular prevent successful grafting. Technique.-Thorough hasmostasis should be obtained to prevent haematoma, one of the commonest causes of failure; while careful dressing is important as faulty immobilisation will allow the graft to slip and tear the vascular attachments.
Drugs.-Cortisone diminishes the chances of a graft thriving, presumably by retarding mitosis and cellular growth of new vessels (Dempster 1956). If the underlying cause of failure is inadequate oxygenation of the graft, by increasing the oxygen tension, and thus correcting hypoxia, it might be possible to sustain it until an adequate circulation has developed. While treating patients with hyperbaric oxygen for ischaemic skin flaps and pedicles (Perrins 1966), it was noted that the split skin grafts used to cover the donor areas survived particularly well. A controlled trial was performed to confirm this impression. Method
Selection of Patients Since so many factors influence the survival of split skin grafts, it is impossible to pair even similar patients. Every patient that presented for split skin grafting was therefore included, regardless of age (except infants), sex and thickness, size, or situation of the graft, or the underlying cause of the lesion. Allocation of Patients Patients were allotted randomly to treatment or control groups. Routine surgery was performed by Mr. A. J. Evans who did not know if the case was subsequently to be treated. All cases had closed dressings of paraffin gauze, Fig. 3-Case 1: (A) burn eschar before
dressing.
operation ;and (B) split
skin grafts at second
cotton
wool, and bandages applied
operation
and donor sites.
to
the
870
Fig. 4-Case 2: (A) hypertrophic burns scarring; (B)
appearance at
Schedule of Treatment The patients to be treated were placed in a Vicker’s clinical transparent pressure chamber (Williams and Hopkinson 1965) and given 100% oxygen at 2 atmospheres absolute (= 14-7 lb. per sq. in.) for 2 hours on the evening of operation and thereafter in the morning and evening for three days. Estimation of Results Patch grafts.-The number of patches applied to the raw area were counted at operation; and on the 7th day, when the second dressing was performed, an estimate was made of those that were soundly attached and healthy. Sheet grafts.-The area grafted was outlined on sterile ’Cellophane’ and a similar outline made of the areas that were covered by permanently healthy graft. The cellophane representing a successful " take " was cut out, weighed, and subtracted from the whole. Thus the percentage survival was obtained. Results 48 patients were included in the trial, half being treated
and half serving as controls. Details of the results are given in fig. 2. Consistently better results were observed in the treated group, but two grafts failed completely. One was found to be heavily infected with P-hæmolytic and in the other the patient had been streptococci " covered " with cortisone at operation. If these two
Fig. 5-Case 3: (A) after four earlier attempts
at skin
discharge from hospital;
and
(C) appearance
a
year later.
"
excluded on the grounds that a successful " take could not be expected, an improvement of 29% in survival of the surface area of the grafts was achieved. Complete survival (i.e., 95% " take " or over) occurred in 64% as cases are
to 17% of the controls. Over 80% of the grafted area survived in nearly twice as many of the treated cases as in the controls; while in none of the treated cases was less than a 60% "take" obtained (see table).
opposed
Significance Tests Including the two failed cases, the two mean values of permanent graft survival are 84-2% for the treated group and 62-7% for the control group (Student’s t=2-92 A Wilcoxon two-sample test, which might be p<0.01). preferable in view of the asymmetry of the distribution of the results, leads
to a
similar conclusion. If the failed
excluded, the means are 91-7% for the treated group and 62-7% for the controls (t=4.31, p<0.001). The effect of treatment is, thus, highly significant. cases are
Case-reports Case 1, Male, Aged 66 (fig. 3) He caught his trousers alight and was admitted with fullthickness burns of most of the left leg, estimated at 15% of the
grafting;
and (B) after fifth attempt with aid of hyperbaric oxygen.
871 area. The sloughs were excised after 14 days and days after the accident the raw area was deemed suitable for grafting. Split skin grafts were taken from the unburnt leg, and the patient treated with hyperbaric oxygen, 2 atmospheres absolute, for 2 hours morning and evening for 31/2 days. When the graft was inspected at the second dressing 7 days later take had occurred. a 100% Case 2, Male, Aged 12 (fig. 4) He was burnt about the neck and chin during a school
body-surface 30
"
Case 3, Male, Aged 64 (fig. 5) He had rheumatoid arthritis affecting most of his joints, and had been bedridden for some years. A pressure sore developed over the left external maleolus of the tibia and four attempts at skin grafting had failed before he was referred to the plastic surgical unit. A split skin graft was again applied and he was treated twice daily at 2 atmospheres absolute for 3 days. Complete skin cover was achieved, and the graft remained stable for 2 months, when he died from a perforated duodenum.
Discussion
These results show that improved survival can be obtained in split skin grafting by correcting the hypoxia present during the first few days after operation. It is reasonable to suppose that the beneficial effects of hyperbaric oxygen would cease a few minutes after return to a normal atmosphere-unless a depot of oxygen had been created, which seems unlikely. Since the oxygen consumption of skin is only 0-33 ml. per 100 g. of tissue per minute (Bard 1956), the requirements of a graft must be very low, so a reasonable explanation would be that the skin can survive for several hours in a hypoxic condition, and that intermittent correction prolongs this period
indefinitely. It must be
emphasised
that
whole-body
exposure
was
used. It would be interesting to repeat the investigation in a large chamber with the patient breathing air while the is
G. E. MAVOR M.A., Ch.M. Aberd., M.D. Rochester, F.R.C.S.E. CONSULTANT SURGEON
"
chemistry lesson. After grafting, a disfiguring hypertrophic scar developed and 8 months after the accident this was excised and a thick split skin graft applied. He was treated with hyperbaric oxygen at 2 atmospheres absolute for 2 hours thrice daily for 3 days, and when the dressings were removed, the whole graft had survived.
graft
THE ILIOFEMORAL VENOUS SEGMENT AS A SOURCE OF PULMONARY EMBOLI
exposed
to
oxygen, and thus
determining
if
increased diffusion through the epithelial surface is responsible for the effect. It is, of course, possible that the increased oxygen tension in compressed air alone sufficient. The ideal exposure to hyperbaric oxygen has yet to be determined: in this series 2 atmospheres absolute was routinely used, since intermittent exposure at this pressure presents little, if any, pulmonary or neurological hazard to the patient. 2-hour treatments on the evening of the operation and twice daily thereafter for 3 days resulted in a significant improvement in survival. Less frequent and shorter exposures at lower pressures might prove as satisfactory, but perhaps more intensive treatment might improve the results even further. In case 2 particularly satisfactory results were achieved with a thick graft by exposure three times a day. This case suggests that the scope of large thick split skin grafts might be extended in reconstructive surgery to situations where otherwise there would be no alternative to multistage transfer
might prove
procedures. I thank Mr. A. J. Evans, F.R.C.S., for encouraging me to treat his patients; and Prof. Peter Armitage of the London School of Hygiene and Tropical Medicine and Dr. A. McPherson of the Medical Research Council for supervising the statistical methods.
J. M. D. GALLOWAY M.B. Edin., F.R.C.S.E. SURGICAL REGISTRAR
ABERDEEN ROYAL INFIRMARY
The
a venous segment is of pulmonary emboli, detectable on clinical examination in a high proportion of cases if signs of thrombosis high up in the leg, particularly groin tenderness, are sought. The iliofemoral segment can also be the source of embolism in cases without demonstrable signs when thrombosis is incomplete. An essential part of management lies in securing precise knowledge of the state of the iliofemoral segments, which can be readily obtained by means of bilateral femoral venography.
Summary
iliofemoral
common
source
Introduction THE source of pulmonary emboli is generally agreed to be the deep veins of the legs and to a lesser extent, the veins of the pelvis and abdomen (British Medical Journal 1966). This vague description has led to considerable confusion, but it is now generally accepted that emboli arise from the veins of the calf or from tributaries of the internal iliac vein to the exclusion of other sites, and treatment is accordingly decided on this assumption. Venographic studies (Bauer 1940) and the common finding of thrombus in the venous sinuses of the calf muscles (Cotton and Clark 1965, Murley 1950) support the view that clotting originates in the veins of the calf. The venous plexuses of the pelvic organs also are commonly the site of thrombus formation. Nevertheless, clotting at these sites, though common, is seldom followed by pulmonary embolism and the evidence that they are a significant cause of embolism is incomplete. Many years ago Aschoff (1924) pointed out that the internal-iliac system, while often the site of thrombosis, could not give rise to major pulmonary embolism. Sevitt (1960), by careful dissection of the veins of the pelvis and all the veins of the leg, showed that there were six common sites of thrombus formation-the external iliac veins just above the inguinal ligament, the common femoral vein, the termination of profunda femoris vein, the popliteal vein at the adductor hiatus, the posterior tibial veins, and the soleal sinuses. Often, clotting was present at two or more sites independently. Gibbs (1957) reported that the calf veins were the commonest site of thrombosis, but that most emboli originated in the thigh or iliac veins, and McLachlin and Paterson (1951) reported that 73% of thrombi began in veins of the thigh or iliac veins and that 56% of the patients affected had an MR. PERRINS: REFERENCES
Bard, P. (1956) Medical Physiology; p. 221. London. Conway, H., Stark, R. B., Joslin, D. (1951) Plast. reconstr. Surg. 8, 312. Dempster, W. J. (1956) An Introduction to Experimental Surgical Studies; p. 23. Oxford. Jackson, D. M. (1961) in Wound Healing (edited by D. Sloame); p. 82. Oxford.
Perrins, D. J. D. (1966) in Hyperbaric Medicine (edited by I. W. Brown and B. G. Cox); p. 613. Washington, D.C. Sevitt, S. (1957) Burns; p. 68. London. Williams, K. G., Hopkinson, W. I. (1965) in Hyperbaric Oxygenation (edited by I. McA. Ledingham); p. 373. Edinburgh. Wolff, K., Schellander, F. G. (1965) J. invest. Derm. 48, 38.
purging with large amounts of magnesium sulphate, both potent cholecystagogues, strongly suggests that V. cholerce may be harboured in the gallbladder during convalescence. In studies with the canine cholera model system Dr. R. B. Sack (personal communication) has had a single dog which continued to excrete vibrio intermittently in his stool without purge for 120 days during convalescence. At open surgery on the 56th day, the gallbladder was cultured by aspiration and 1000 vibrios per ml. were grown from the bile. Case 1 demonstrated all rough vibrios on the last three positive vibrio cultures. This corroborates a clinical impression that shortly before a patient becomes vibriofree the organism occasionally changes its morphological or antigenic character. It is generally believed that the vibrio is a rough non-pathogenic one. We are continuing to examine the patient in case 1 whose stools continued to yield vibrios, after purging, for at least 174 days. He last excreted vibrios which produced only smooth colonies on the 44th day after his last clinical symptom of cholera. The relative efficacy of the various antibiotic regimens used will be reported elsewhere. It is perhaps significant that the two positive patients were in the control group and received no antibiotics. We elected not to treat them subsequently to establish the duration of vibrioculture positivity. The value of antibiotics in preventing the convalescent carrier state or in treating carriers has not been determined. MacKenzie (1965) and Tamayo et al. (1965) have reported a very high incidence of symptom-free carriers in the recent cholera pandemic due to biotype El Tor. Mukerjee et al. (1965), among others, believe that V. cholerœ biotupe El Tor behaves differently from the classical vibrio, and considered it to be responsible for a different epidemiological pattern than that seen in previous cholera pandemics. Our findings do not confirm nor refute these opinions, but they do indicate that an inapparent carrier state may be present in the convalescent patient infected with V. cholerœ biotype El Tor. We thank Dr. R. N. Chaudhuri (former director) and Dr. J. B. Chatterjee, director, of the Calcutta School of Tropical Medicine, and their staffs; Dr. P. M. Manji, superintendent, and Prof. A. Das, clinical director, of the Infectious Diseases Hospital, and their staffs, for continued interest, advice and support of this study; and Dr. J. L. Boyer who was especially helpful in initiating this work. This work was supported in part by U.S. Public Health Service research grant no. H26. 6114 and in part by finding under Public to
gallbladder which emptied satisfactorily after cholecystokinin. In case 2, the gallbladder was not visualised even after a double dose of iopanoic acid (’ Telepaque ’). normal
INFLUENCE OF HYPERBARIC OXYGEN ON THE SURVIVAL OF SPLIT SKIN GRAFTS D. RESEARCH
J. D. PERRINS
M.B. Cantab., F.R.C.S. REGISTRAR, BURNS UNIT, QUEEN MARY’S HOSPITAL, ROEHAMPTON, LONDON S.W.15*
The possibility of obtaining increased survival of split skin grafts by the use of hyperbaric oxygen was investigated in a controlled clinical trial. This showed that a significant improvement can be obtained. In this series an increase in survival of 29% of the surface area of the grafts was achieved. A high proportion of complete " takes occurred; 64% of the treated cases as opposed to 17% of the controls. The results suggest that the method is valuable when extensive raw areas have to be covered, or when good cosmetic results are important. Summary
"
Introduction
of the fate of split skin grafts is not only of academic interest. Jackson (1961) stated that " the problem of successful closure of wounds with free split skin grafts is one of the important practical issues of wound " healing today. At present the average permanent " take of skin grafts on large open wounds, whether excised or granulating, is about 75%. This is clearly no ground for satisfaction and calls for improved technique and further basic research." In the patient with extensive burns it is important to obtain skin cover if life is to be saved, while the shortage of donor sites makes the survival of available skin doubly important. A
STUDY
Natural History of Skin Grafts The blood-vessels of a skin graft, after its removal from the donor site, are in a state of collapse and contain no red blood-
Law
480, section 104 (c), agreement no. 5x4317. Requests for reprints should be addressed to C.
K. W.
REFERENCES
Cole, J., Greenough, III, W. B. (1965) Lancet, ii, 972. Gangarosa, E. J., Saghari, H., Emile, J., Siadat, H. (1966) Bull. Wld Hlth Org. 34, 363. Greig, E. D. W. (1914) Indian J. med. Res. 2, 28. Kulesha, G. S., (1911) Patologicheskoi Anatomii Aziatskoi Kholery. St. Petersburg. MacKenzie, D. J. M. (1965) Publ. Hlth Serv. Publs, Wash. no. 1328, p. 341. Mukerjee, S., Basu, S., Bhattacharga, P. (1965) Br. med. J. ii, 837. Nikonov, A. G. (1958) J. Microbiol. Epidem. Immunol. 29, 40. Pollitzer, R. (1959) Monogr. Ser. W.H.O. no. 43. Rogers, L. (1952) Tropical Medicine (edited by L. Rogers and D. J. W. Megaw); p. 273. Simmonds, M. (1892) Dt. med. Wschr. 18, 931. Tamayo, J. F., Mosley, W. H., Alvero, M. G., Joseph, P. R., Gomez, C. Z., Montague, T., Dizon, J. J., Henderson, D. A. (1956) Bull. Wld Hlth Org. 33, 645. Valk, W. (1915) Geneesk. I. Ned.-Ind. 55, 561. Wallace, C. K., Carpenter, C. C. J., Mitra, P. P., Sack, R. B., Khanra, S. K., Werner, A. S., Duffy, T. P., Oleinick, A., Lewis, G. W. (1965) Trans. R. Soc. Trop. Med. Hyg. 59, 621.
Addendum
performed on Feb. 20, 1967. In normal visualisation of an apparently
Cholecystography case
1, there
was
was
1-Model of healing process of split skin grafts showing phases regression and recovery of enzyme activity (succinic dehydrogenase). (Wolff and Schellander 1965.)
Fig.
of
but recover at about 24 hours. They then dilate and contain fibrinogen-free fluid which quickly passes out into the substance of the graft to meet the metabolic requirements for several days. During this period of ischamua there is a low oxygen tension in the cells of the graft which is responsible for depression of mitotic activity (Dempster 1956). At about 48 hours vascular connection between the graft and its bed begins and is followed by fibroblastic invasion. By the fifth day the graft is well vascularised, mitotic activity returns as the result of the correction of hypoxia and is associated with hypertrophy and thickening of the epidermis, which continues
cells,
*
Present address: Institute of Orthopædics, Hospital, Stanmore, Middlesex.
Royal National Orthopiced
869
activity. The arrow indicates level at which the operation was performed. The first 4 days are characterised by a decline of enzyme activity, starting at the dermoepidermal junction and progressing to the deeper portion of the graft; the critical point occurring by the fourth day, when revascularisation starts and enzyme activity progresses to the dermoepidermal junction. Factors Influencing the Success of Split Skin Grafting The successful " take " of a split skin graft is finally dependent on its vascularisation from the underlying bed, and any factor impeding this ingrowth will mitigate against success. Clinical experience has shown that the following factors are important. Age.-The older the patient the more likelihood of a sclerotic blood-supply to the part. Anœmia.—The oxygen-carrying capacity of the blood must be
adequate to sustain the graft. The character of the recipient site.-A healthy viable base is required with no necrotic tissue, exposed tendon, or bone.
PROPORTION OF TREATED AND CONTROL CASES IN RELATION TO GRAFT SURVIVAL
Fig. 2-Survival of split skin grafts
in treated and control groups.
increase until the sixteenth day, when a peak is reached in capillary invasion and cellular hyperplasia (Conway et al. 1951, Sevitt 1957). Elegant enzyme-histochemical studies have revealed a striking decline in enzyme activity in split skin grafts during the first postoperative days (Wolff and Schellander 1965). If enzyme activity is a measure of oxidative metabolism, such studies reflect the degree and progression of hypoxia in the graft. Fig. 1 shows Wolff and Schellander’s (1965) model. The segments represent normal skin and specimens taken on the lst to the 20th postoperative day. Shades of grey and black indicate intensity and distribution of succinic-dehydrogenase
to
Overall improvement 29 % (mean value of permanent graft survival of 91’7% in treated group less 62’7% in the controls).
Fresh granulations’ provide better vascularisation than those that have been present for some time. Infection.-Group A &bgr;-hæmolytic streptococci and Pseudomonas pyocynea in particular prevent successful grafting. Technique.-Thorough hasmostasis should be obtained to prevent haematoma, one of the commonest causes of failure; while careful dressing is important as faulty immobilisation will allow the graft to slip and tear the vascular attachments.
Drugs.-Cortisone diminishes the chances of a graft thriving, presumably by retarding mitosis and cellular growth of new vessels (Dempster 1956). If the underlying cause of failure is inadequate oxygenation of the graft, by increasing the oxygen tension, and thus correcting hypoxia, it might be possible to sustain it until an adequate circulation has developed. While treating patients with hyperbaric oxygen for ischaemic skin flaps and pedicles (Perrins 1966), it was noted that the split skin grafts used to cover the donor areas survived particularly well. A controlled trial was performed to confirm this impression. Method
Selection of Patients Since so many factors influence the survival of split skin grafts, it is impossible to pair even similar patients. Every patient that presented for split skin grafting was therefore included, regardless of age (except infants), sex and thickness, size, or situation of the graft, or the underlying cause of the lesion. Allocation of Patients Patients were allotted randomly to treatment or control groups. Routine surgery was performed by Mr. A. J. Evans who did not know if the case was subsequently to be treated. All cases had closed dressings of paraffin gauze, Fig. 3-Case 1: (A) burn eschar before
dressing.
operation ;and (B) split
skin grafts at second
cotton
wool, and bandages applied
operation
and donor sites.
to
the
870
Fig. 4-Case 2: (A) hypertrophic burns scarring; (B)
appearance at
Schedule of Treatment The patients to be treated were placed in a Vicker’s clinical transparent pressure chamber (Williams and Hopkinson 1965) and given 100% oxygen at 2 atmospheres absolute (= 14-7 lb. per sq. in.) for 2 hours on the evening of operation and thereafter in the morning and evening for three days. Estimation of Results Patch grafts.-The number of patches applied to the raw area were counted at operation; and on the 7th day, when the second dressing was performed, an estimate was made of those that were soundly attached and healthy. Sheet grafts.-The area grafted was outlined on sterile ’Cellophane’ and a similar outline made of the areas that were covered by permanently healthy graft. The cellophane representing a successful " take " was cut out, weighed, and subtracted from the whole. Thus the percentage survival was obtained. Results 48 patients were included in the trial, half being treated
and half serving as controls. Details of the results are given in fig. 2. Consistently better results were observed in the treated group, but two grafts failed completely. One was found to be heavily infected with P-hæmolytic and in the other the patient had been streptococci " covered " with cortisone at operation. If these two
Fig. 5-Case 3: (A) after four earlier attempts
at skin
discharge from hospital;
and
(C) appearance
a
year later.
"
excluded on the grounds that a successful " take could not be expected, an improvement of 29% in survival of the surface area of the grafts was achieved. Complete survival (i.e., 95% " take " or over) occurred in 64% as cases are
to 17% of the controls. Over 80% of the grafted area survived in nearly twice as many of the treated cases as in the controls; while in none of the treated cases was less than a 60% "take" obtained (see table).
opposed
Significance Tests Including the two failed cases, the two mean values of permanent graft survival are 84-2% for the treated group and 62-7% for the control group (Student’s t=2-92 A Wilcoxon two-sample test, which might be p<0.01). preferable in view of the asymmetry of the distribution of the results, leads
to a
similar conclusion. If the failed
excluded, the means are 91-7% for the treated group and 62-7% for the controls (t=4.31, p<0.001). The effect of treatment is, thus, highly significant. cases are
Case-reports Case 1, Male, Aged 66 (fig. 3) He caught his trousers alight and was admitted with fullthickness burns of most of the left leg, estimated at 15% of the
grafting;
and (B) after fifth attempt with aid of hyperbaric oxygen.
871 area. The sloughs were excised after 14 days and days after the accident the raw area was deemed suitable for grafting. Split skin grafts were taken from the unburnt leg, and the patient treated with hyperbaric oxygen, 2 atmospheres absolute, for 2 hours morning and evening for 31/2 days. When the graft was inspected at the second dressing 7 days later take had occurred. a 100% Case 2, Male, Aged 12 (fig. 4) He was burnt about the neck and chin during a school
body-surface 30
"
Case 3, Male, Aged 64 (fig. 5) He had rheumatoid arthritis affecting most of his joints, and had been bedridden for some years. A pressure sore developed over the left external maleolus of the tibia and four attempts at skin grafting had failed before he was referred to the plastic surgical unit. A split skin graft was again applied and he was treated twice daily at 2 atmospheres absolute for 3 days. Complete skin cover was achieved, and the graft remained stable for 2 months, when he died from a perforated duodenum.
Discussion
These results show that improved survival can be obtained in split skin grafting by correcting the hypoxia present during the first few days after operation. It is reasonable to suppose that the beneficial effects of hyperbaric oxygen would cease a few minutes after return to a normal atmosphere-unless a depot of oxygen had been created, which seems unlikely. Since the oxygen consumption of skin is only 0-33 ml. per 100 g. of tissue per minute (Bard 1956), the requirements of a graft must be very low, so a reasonable explanation would be that the skin can survive for several hours in a hypoxic condition, and that intermittent correction prolongs this period
indefinitely. It must be
emphasised
that
whole-body
exposure
was
used. It would be interesting to repeat the investigation in a large chamber with the patient breathing air while the is
G. E. MAVOR M.A., Ch.M. Aberd., M.D. Rochester, F.R.C.S.E. CONSULTANT SURGEON
"
chemistry lesson. After grafting, a disfiguring hypertrophic scar developed and 8 months after the accident this was excised and a thick split skin graft applied. He was treated with hyperbaric oxygen at 2 atmospheres absolute for 2 hours thrice daily for 3 days, and when the dressings were removed, the whole graft had survived.
graft
THE ILIOFEMORAL VENOUS SEGMENT AS A SOURCE OF PULMONARY EMBOLI
exposed
to
oxygen, and thus
determining
if
increased diffusion through the epithelial surface is responsible for the effect. It is, of course, possible that the increased oxygen tension in compressed air alone sufficient. The ideal exposure to hyperbaric oxygen has yet to be determined: in this series 2 atmospheres absolute was routinely used, since intermittent exposure at this pressure presents little, if any, pulmonary or neurological hazard to the patient. 2-hour treatments on the evening of the operation and twice daily thereafter for 3 days resulted in a significant improvement in survival. Less frequent and shorter exposures at lower pressures might prove as satisfactory, but perhaps more intensive treatment might improve the results even further. In case 2 particularly satisfactory results were achieved with a thick graft by exposure three times a day. This case suggests that the scope of large thick split skin grafts might be extended in reconstructive surgery to situations where otherwise there would be no alternative to multistage transfer
might prove
procedures. I thank Mr. A. J. Evans, F.R.C.S., for encouraging me to treat his patients; and Prof. Peter Armitage of the London School of Hygiene and Tropical Medicine and Dr. A. McPherson of the Medical Research Council for supervising the statistical methods.
J. M. D. GALLOWAY M.B. Edin., F.R.C.S.E. SURGICAL REGISTRAR
ABERDEEN ROYAL INFIRMARY
The
a venous segment is of pulmonary emboli, detectable on clinical examination in a high proportion of cases if signs of thrombosis high up in the leg, particularly groin tenderness, are sought. The iliofemoral segment can also be the source of embolism in cases without demonstrable signs when thrombosis is incomplete. An essential part of management lies in securing precise knowledge of the state of the iliofemoral segments, which can be readily obtained by means of bilateral femoral venography.
Summary
iliofemoral
common
source
Introduction THE source of pulmonary emboli is generally agreed to be the deep veins of the legs and to a lesser extent, the veins of the pelvis and abdomen (British Medical Journal 1966). This vague description has led to considerable confusion, but it is now generally accepted that emboli arise from the veins of the calf or from tributaries of the internal iliac vein to the exclusion of other sites, and treatment is accordingly decided on this assumption. Venographic studies (Bauer 1940) and the common finding of thrombus in the venous sinuses of the calf muscles (Cotton and Clark 1965, Murley 1950) support the view that clotting originates in the veins of the calf. The venous plexuses of the pelvic organs also are commonly the site of thrombus formation. Nevertheless, clotting at these sites, though common, is seldom followed by pulmonary embolism and the evidence that they are a significant cause of embolism is incomplete. Many years ago Aschoff (1924) pointed out that the internal-iliac system, while often the site of thrombosis, could not give rise to major pulmonary embolism. Sevitt (1960), by careful dissection of the veins of the pelvis and all the veins of the leg, showed that there were six common sites of thrombus formation-the external iliac veins just above the inguinal ligament, the common femoral vein, the termination of profunda femoris vein, the popliteal vein at the adductor hiatus, the posterior tibial veins, and the soleal sinuses. Often, clotting was present at two or more sites independently. Gibbs (1957) reported that the calf veins were the commonest site of thrombosis, but that most emboli originated in the thigh or iliac veins, and McLachlin and Paterson (1951) reported that 73% of thrombi began in veins of the thigh or iliac veins and that 56% of the patients affected had an MR. PERRINS: REFERENCES
Bard, P. (1956) Medical Physiology; p. 221. London. Conway, H., Stark, R. B., Joslin, D. (1951) Plast. reconstr. Surg. 8, 312. Dempster, W. J. (1956) An Introduction to Experimental Surgical Studies; p. 23. Oxford. Jackson, D. M. (1961) in Wound Healing (edited by D. Sloame); p. 82. Oxford.
Perrins, D. J. D. (1966) in Hyperbaric Medicine (edited by I. W. Brown and B. G. Cox); p. 613. Washington, D.C. Sevitt, S. (1957) Burns; p. 68. London. Williams, K. G., Hopkinson, W. I. (1965) in Hyperbaric Oxygenation (edited by I. McA. Ledingham); p. 373. Edinburgh. Wolff, K., Schellander, F. G. (1965) J. invest. Derm. 48, 38.