Bums
(1992)
18, (5), 395-400
Printed in Great Britain
395
Fibrin glue in the treatment of dorsal hand burns W. Boeckx, M. Vandevoort, Ph. Blondeel, D. Van Raemdonck and E. Vandekerckhove Bum Centre, K. I-J. Louvain, Belgium
This paper analyses two groups of patients with only dorsal hand burns: groups I contains patients with a total of 15 burned hands ana’group I1 patients with 12 hand burns. The patients ingroup I were all treated by full sheet skin grafts using a two-component fibrin glue. Patients in group I1 undetwent Ihe traditional operative freatment without fibrin glue and the same postoperativephysical therapy programme. After follow-up periods of 6-11 months dgfoup I) and 12-21 months &oup II], we investigated in both groups, grip strength, key pinch, mobility, two-point discrimination and with the Semmes-Weinstein monofilaments. Our results prove &af after Ihe respective follow-up periods group I patients developed far better results for two-point discrimination, touch recognition and mobility.
History As early as 1915 successful experiments were reported by Grey (1915) with fibrin as a sealant and haemostatic agent for the control of haemorrhage in certain types of intracranial surgery. In 1940 Young and Medawar (1944) used it for peripheral nerve repair. In the mid-1940s Katzin (1945) reported the use of aqueous fibrin for the fixation of penetrating cornea1 grafts in rabbits. In 1943 Tidrick and Warner (1944) described a method for aiding the adhesive process in the grafting of skin. One year later, Cronkite et al. (1944) confirmed the technique - in which the skin transplant was immersed in a solution of titrated plasma, saturating the surface with fibrinogen, and then placing it on the recipient site after coating the tissue with a commercially prepared thrombin solution - as being superior, having extremely short binding time and achieving a solid mechanical bond. Furthermore the general healing process was speeded up by this technique. A JO-year hiatus then ensued while the idea lay dormant, probably because one factor limited the use of fibrin-based adhesions, namely the need to obtain fresh plasma from the recipient. In 1972 Mahas et al. introduced commercially prepared fibrin glue for peripheral nerve repair. From that time, fibrin glue has gained popularity as a biological adhesive among the surgical specialties, and has been reported to be a safe bioadhesive and sealant. Nowadays fibrin glue (Tissucol - Tisseel) is made from pooled human plasma obtained from licensed plasmapheresis centres in Central Europe. All donors are well known. They accept the need for clinical and biological follow-up. Donors are tested at every donation for HBS antigen using 0 1992 Butterworth-Heinemann 0305-4179/92/050395-06
Ltd
radioimmunoassay and for HIV antibody. To reduce the risk of non-A/non-B hepatitis transmission only plasma with alanine aminotransferase (ALT) levels below 25 U/litre are used for manufacturing fibrin sealant. Additionally thermoviro inactivation ensures a high degree of safety and avoids viral transmission. Currently the transmission of hepatitis B, hepatitis non-A/non-B and possibly AIDS has not been reported in the European literature. Alternatively the use of autologous fibrin tissue adhesive completely eliminates the danger of transmitting viral infections because component 1 (fibrinogen and aprotinin) is derived from the patient’s own blood (Panis and Scheele, 1981; Scheele and Schricker, 1981; Siedentop et al., 1985, 1987; Eder et al., 1986; Chakravorty and Sosnowski, 1989; Saltz et al., 1989; Stuart et al., 1990).
Physiology Fibrin glue, a biological product, mirrors the final common pathway of the normal coagulation cascade (von Seelich and Redl, 1979; Dresdale et al., 1985; Hilfinhaus and Weidmann, 1985; Tisseel, 1985; Ellis and Pelausa, 1988; Ellis and Shaikh, 1990). Fibrinogen, when combined with thrombin, develops loose monomeric fibrin. The presence of factor XIII (Grey, 1915) and calcium causes monomeric fibrin to polymerize lengthwise between the recipient and the skin graft forming a rapid and strong mechanical bond which results in the fibrin glue matrix. The normal degradation of this glue matrix by plasmin is blocked by aprotinin (Trasylol), an antiprotease, thus prolonging its sealant action (Fi’re I). The biochemical action of commercially prepared fibrin glue will result in sealing and bonding tissue and promoting haemostasis and wound healing. Thrombin Fibrinogen
LFibrin
Factor
XIII + Ca Fibrin
(monomer)
(polymer)
I Plasmin
-1
t Aprotinin I Fibrin
Figure 1. Schema showing fibrin.
the formation
degradation
and degradation
of
396
Bums (1992) Vol. IS/No.
5
160 ?? 140
12345678
9
10
11
12
13
14
15
Patients (no.) Figure 3. Key pinch: mean fibrin glue, 98.68 per cent; mean control, 92.99 per cent. 0.5 > P> 0.1. 1, Fibrin glue; 0, control. III 234567%
II
III 9
II 10 11
III 12 13
14
1 15
Patients (no.) Figure 2. Grip strength: mean fibrin glue, 84.45 per cent; mean control, 86.97 per cent. P> 0.5. ?? , Fibrin glue; 0, control.
?? ?? 0
0
?? ??
?? 2.5 0
2.0
0
w
??
??
0
i.5
0
?? ??
0
1.0
0
’
11
11
I
1 9
I 10
I 11
I 12
III 13 14
15
??
Patients (no.) Figure 5. Two-point discrimination on the dorsum of the fingers. Mean fibrin glue, 1.01 cm; mean control, 1.39 cm. 0.05 > P> 0.02. ?? , Fibrin glue; 0, control.
m
/
01
ot ! I 12345678
1
12345678
’
“1
11
9
1
10
’
11
11
12
13
11
14
15
Patients (no.) Figure 4. Two-point discrimination on the dorsum of the hand: mean fibrin glue, 1.33 cm; mean control, 2.18 cm. 0.01 > P> 0.001. H, Fibrin glue: 0, control.
Methods and operating technique The aim of this study was to provide clinical proof of firmer graft adhesion, better sensibility of the burned hand after grafting and a better functioning grafted hand with this technique using fibrin glue. For these reasons we used only the dorsal sites on burned hands. Surgery was performed on all patients within 1 week postbum. All patients required non-meshed split skin grafts of 0.010-0.012 in (0.25-0.28mm) taken by an electric dermatome. The recipient site was then stretched and denuded as much as possible with the electric dermatome and McGulian until a well-bleeding surface appeared. The most important bleeding spots were coagulated. The graft was cut to shape.for an accurate fit, followed by insertion of a few reinforcement sutures (vicryl4-0). Two separate solutions containing: (I) fibrinogen and aprotinin, and (2) thrombin and calcium, were mixed
(Tisseel, 1985; Cuny et al., 1986; Ellis and Pelausa, 1988), using a combined heating and stirring device (the fibri-
notherrn) to stir the components and maintain a temperature of 37°C. Once a viscous consistency was attained the fibrinogen concentrate and reconstituted thrombin were drawn in sterile syringes and locked in the duplojet dip. A common piston ensured equal volumes of fibrinogen and thrombin were mixed and ejected. Then, using the Tissumat pressure-regulator, the two-component tissue glue was sprayed on the recipient site as well as on the recipientcontact site of the graft which was already partially attached (see above). The graft was then placed in position and the remaining reinforcement sutures were inserted. On the fifth postoperative day the bandages were taken off. Only the successfully grafted hands were included in this study. Patients
During a 5-month period from December 1989 to April 1990 patients with a total of 15 dorsal hand bums (group I) were admitted to the bum unit of the St Pieter University Hospital, Louvain. The causes of these hand bums were: thermal (86.6 per cent), and electrical (13.3 per cent). The patient’s age distribution ranged from 8 to 40 years (mean of 31 years). The average TBSA bum was 15 per cent. Patients in this first group were all treated using ,the two-component tissue glue. A control group (group II) of patients with a total of 12 dorsal hand bums had been admitted in our hospital during
Boeckx et al.: Fibrin glue in treatment of dorsal hand bums
I
I
2.83
3.61
4.31
397
mJ
2.83
3.61
4.31
4.56
6.65
6.65
Log force
Log force Figure 6. Semmes-Weinstein monofilaments on the dorsal surface of the hand. Mean fibrin glue, 3.83 log force; mean control, 4.41 log force. 0.5 > P> 0.1. ?? , Fibrin glue; 0, control.
Figure 7. Semmes-Weinstein monofilaments on the dorsal surface of the fingers. Mean fibrin glue, 3.35 log force; mean control, 4.08 log force. 0.5 > P> 0.1. ?? , Fibrin glue; @, control.
the previous 9 months, March 1989 to November 1989. In this group all the patients sustained thermal bums with an average TBSA bum of 16 per cent. The patients’ ages ranged from 26 to 57 years with a mean of 35 years. The patients’ hands were all treated with non-meshed split skin grafts of 0.012-0.012 in. (0.25-0.28 mm) taken by an electric dermatome. In both study groups only successfully grafted hands were included. None of the patients included in this study had neurological problems, either before or after the bum accident. The only difference between the patients in the control group and in the test group was the use of the two-component tissue glue to spray on the recipient site and on the recipient-contact site of the graft of the test group patients. All other methods of treatment were identical.
the same type of splinting technique. All patients were fitted with a custom-made pressure glove after the hand had stabilized.
Management
In all patients the bums were diagnosed as deep partial or full skin thickness, and were not expected to heal without surgical intervention (Parry, 1989; Sherif and Sato, 1989). The operation was carried out between 3 and 5 days after burning. Physiotherapy, using the same rehabilitation programme in all patients, started on the day of admission and was carried out in both groups by the same physiotherapist. On day 5 post operation active range of motion (ROM) exercises were begun. Active assisted exercises (with progressively increasing intensity) were started on the day of admission and day 5 postoperation. Splinting of the hand was performed on the day of admission and again during each night from day 5 postoperation in both groups with
Figure 8. Clinical result of a fibrin glue treated hand after 5 days; a perfect take of the graft with only a few bleeding spots left.
Results The follow-up period ranged from 6 to 11 months in the fibrin glue group and from 12 to 21 months in the control group. After these periods all the patients underwent tests to investigate strength, sensibility and mobility. Strength
Grip strength and key pinch were measured. Each of the tests used the methods described by Agnew and Maas (1982) and Mathiowetz et al. (1985, 1986). The patients’ performances were then compared to the average clinical norms related to sex and age (Mathiowetz et al., 1985,1986) and expressed as percentages of the mean values. Figure2 shows that no significant differences were found between the two groups of patients, although even the data for the traditional grafting technique (control group) showed better results (mean 87.0 per cent) than the technique using fibrin glue (mean 84.4 per cent). Probably this is due to the longer follow-up period of the patients in the control group. However, the results for key pinch (Figure 3) show a slight difference between the two grafting techniques significant at the 0.5 > P > 0.1 level. The data for the hands grafted using the fibrin glue technique (mean 98.7 per cent) show that key pinch recuperation was stronger and much faster than that of
Figure9. Clinical result of a fibrin glue treated hand after 6 months showing a complete recovery of mobility and good aesthetic result.
Bums (1992)Vol. 18/No. 5
398
the group treated by the traditional technique (mean 93.0 per cent). Over 11 months the patients in the fibrin glue group improved with almost complete restoration of key pinch. This is in contrast with the follow-up period of 12-21 months in the control group. In both groups we observed that the general results for the key pinch test accord better with the average clinical norms than the data for the test measuring grip strength. This phenomenon can be explained by the fact that key pinch is a test which involves the use of a much smaller muscle group than that for the grip strength test. Also the hand movement, and thus the skin movement, during which strength is exercised, is a lot easier with the key pinch test. Additionally the key pinch is more important for carrying out normal hand function, certainly as far as delicate movements are concerned. Sensibility The sensibility of the grafted hands was tested using two tests: a two-point discrimination and a test with the Semmes-Weinstein monofilaments (Haymaker and Woodhall, 1953; Parsky and House, 1964; Bell, 1984; Bell and Tomancik, 1987). We applied the five filaments that best represented changes in functional levels of touch recognition. The dorsum of the hand and fingers was examined separately. Significant differences were noticed for twopoint discrimination between the two groups of treated hands. On the dorsum of the hand the differences were even significant at the 0.01> P> 0.001 level with a mean value of 1.33 cm for the fibrin glue-treated hands and 2.10 cm for the hands that received a traditional treatment without fibrin glue (Figure4). Significant differences in two-point discrimination on the dorsum of the fingers between the two groups of treated hands were observed (0.05 > P> 0.02). Far better data in the fibrin glue group (mean 1.01cm) were found compared with the control group (mean 1.39 cm) (Figtlre5). Although there are quite important differences between the two groups, the overall data for the hands treated by fibrin glue are still only fair and even poor in comparison with the values for normal hands according to the American Society for Surgery of the Hand. Two-point < 0.6 cm; discrimination: good, fair, 0.6-1.0 cm; poor, 1.1-1.5 cm. The Semmes-Weinstein monofilaments also give a good idea of the post-traumatic recuperation of the burned hand, especially where touch recognition is concerned. This assesses the two-point discrimination as the amount of tactile stimulus which can be distinguished per square centimetre. The test with the Semmes-Weinstein monofilaments indicates a statistically significant difference in touch recognition between the two groups of treated hands. This touch recognition is expressed in terms of force or log force which needs to be exerted on the skin of the investigated area (Table I). The normal values for the dorsal surfaces of the
hands and fingers are about 2.83 log force. In our studies the fibrin glue-treated hands required a mean of 3.83 log force on the dorsal surface of the hand and 3.35 log force on the dorsal surface of the fingers. The data for the hands treated traditionally had a mean of 4.41 log force on the hand surface and 4.08 log force on the finger surface. These differences between the two groups are both statistically significantly at the 0.5 > I’> 0.1 level(Figttres6, 7) Thus there is a significantly better recovery of sensibility after bums when fibrin glue is used in the operating technique. Mobility Our study also reviewed the mobility of hands with dorsal bums starting from 0” to the utmost flexion. Measurements were made successively with wrist flexion, flexion of the metacarpophalangeal joint (MCP), the proximal interphalangeal joint (PIP) and the distal interphalangeal joint (DIP). For references we used data on hand flexion derived from the four studies shown in TubleII. FigureIOshows the flexion of the fibrin glue-treated hands compared with the mobility of the hands treated traditionally. All numbers marked out in the diagrams are the mean values of the observed data respectively in the two groups of patients. So far as wrist flexion is concerned there was little difference between the two mean values (mean fibrin glue group 70.60” and mean group II 67.83” with 0.5 > P> 0.1). These results reflect our selection of bums affecting only the dorsal surfaces of the hands and fingers. The most marked mean differences are found in the flexion of the MCP joints of all five fingers. The MCP joint is situated on all hands between two burned and therefore treated surfaces. We conclude therefore that the MCP joint is the most important joint to measure the recovery of flexion after bums. This joint showed significant differences at the 0.5 > P> 0.1 level for digit 1, at the 0.1> P> 0.05 level for digit 2, and even at the 0.05 > P> 0.02 level for digits 3,4 and 5. Differences in flexion of the PIP joints are also fairly good and significant: 0.5 > P> 0.1for digits 2 and 3,0.1> P> 0.05 for digit 4 and 0.05> P> 0.02for digit 5. It is striking that between the two groups the difference in flexion of the MCP and PIP joints in digits 3, 4 and 5 is of a greater significance than in digits I and 2. The results for the interphalangeal joint (IP) of digit 1 and the DIP joints of the other four fingers indicate that the more distal the place of the hand bum, the less significant the difference in flexion, findings which probably reflect the fact that the more distal areas of the finger were subject to more minor bums which healed spontaneously in many patients
(Figures8, 9).
Table II References
Table1 Force (9)
0.080 0.217
2.35 4.19 279.4
Log force
2.83 3.61 4.31 4.56 6.65
Wrist flexion MCP PIP DIP
1
2
70” 90 100 70
70 90 100 70”
??
3
4
Mean
90
80 90 100 90
73” 90 100’ 80”
“Journal Medical Association, 1958. Xommittee of California Medical Association, %lark, 1920. ‘The Committee on Joint Motion, 1965.
1960.
Boeckx et al.: Fibrin glue in treatment of dorsal hand burns
MCP:
1
Digit
,j
399
mean fibrin glue 86.66’ mean control 77.08’ 0.5>P > 0.1
\ I,
)
IP:
yea;
DIP:
‘,‘,“,~:,g’,upl$.““”
P > 0.5
/’
Wrist
flexion:
mean fibrin glue mean control 79.91° 0.5 > P> 0.1
\
mean fibrin glue 70.60’ mean control 67.83’ 0.5 > P > 0.1
mean fibrin glue 90.00” mean control 83.75O 0.05 >P > 0.02 Wrist mean
DIP:
mean fibrin glue 80.66’ mean control 78.33’ 0.05 > P > 0.02
flexion: fibrin glue
mean fibrin glue 98.86’ mean control 92.91° 0.5 > P > 0.01
\
\
\
Wrist
\
MCP:
IP:
PIP: 70.60’
mean fibrin glue 89.40° mean control 84.580 0.1 >P > 0.05
mean fibrin glue 98.33’ mean control 93.75O 0.5> P > 0.1
Wrist
DIP: mean fibrin glue 79.86O mean control 78.33’ 0.5 >P > 0.1
d PIP:
Figure 10.
MCP: mean fibrin
glue 90.33O mean control 83.33O 0.05 > P > 0.02
flexion: PIP:
DIP: mean fibrin glue 79.66’ mean control 79.16O / P > 0.5
flexion:
mean fibrin glue 98.33O mean control 93.33’ 0.05 0.1 > P>
\ \ \
MCP: \
/
/
mean fibrin glue 89.66’ mean control 82.50° 00.5> P > 0.02
/
mean fiGin glue 99.40’ mean control 93.33O 0.05 ? P > 0.02
Diagrams
on mobility.
-,
Fibrin
glue; ----,
Discussion In a previous study (Vibe and Pless, 1983) it was suggested that on recipient sites where grafts are subjected to stress movements shortly after placement of the graft survival improved substantially when fibrin glue was used during the operating technique. Our study also indicates that functional recovery after bums is much improved in terms of sensibility, mobility and strength and also the time to reach a certain value of function is increased. This is quite clear when we consider the differences in follow-up period between group I (6-11 months) and group II (12-21 months). Our study also indicated that the use of fibrin glue during the operation is of little benefit for gaining strength after a bum accident. The regaining of strength is more dependent on the time after the bum than on operating technique because muscle tissue is more responsible for exercising strength than epidermis and dermis. A rapid and good healing of the burned skin areas is of great importance for the recuperation of sensibility and mobility. First of all because perception of tactile stimuli depends on the condition of the epidermis and dermis where free sensory nerve endings are abundant and penetrate into the granular layer. Secondly, joint articulation
control.
and muscle working has a less significant effect on mobility than skin elasticity. Therefore the condition of the skin graft, the percentage ‘take’ of the graft and the recovery of elasticity after grafting are extremely important. The operating technique using fibrin glue is faster than the traditional way because only a minimal number of reinforcement sutures are required to fix the graft on the recipient site. In almost all patients it is even possible to work without suture points, it goes without saying however that the importance of good applied bandages cannot be overestimated.
References Agnew P. J. and Maas F. (1982) Hand function related to age and sex. Arch. Phys. Med. Rehabil. 63, 269. Bell J. A. (1984) Semmes-Weinstein monofilaments testing for determining cutaneous light touch/deep pressure sensation. % Star, 44, (2). Bell J. A. and Tomancik L. (1987) The reliability of the SemmesWeinstein monofilaments. 1. Hand Surg. IZA, 155.
400
Bums(1992)Vol.m/No.5
Chakravorty R. C. and Sosnowski K. M. (1989) Autologous fibrin glue in full thickness skin grafting. Ann. Plasf. Surg. 26, 488. Clark W. A. (1920) A system of Joint Movements. 1. Orfhop. Surg. 2, 12. Committee of California Medical Association. The Industrial Accident Committee of the State of California (1960) Evaluation of lndwfriul Disability. Oxford: Oxford University Press. The Committee on Joint Motion (1965) Joint Motion: Method of Measuring and Recording (American Academy of Orthopedic Surgeons.) Edinburgh: Churchill Livingstone. Cronkite E. P., Lozer E. L. and Deaver J. M. (1944)Use of thrombin and fibrinogen in skin grafting. JAMA 124,976. Curry J.-F., Schmutz J.-L., Huber G. et al. (1986) Tissucol et Transglutine: amelioration dans la pratique des greffes cutanees. Ann. Dermufol. Venereal. 113, 739. Dresdale A., Bowman F. O., Malm J. R. et al. (1985) Haemostatic effectiveness of fibrin glue derived from single donor fresh frozen plasma. Ann. I’boruc. Surg. 40,385. Eder G., Neumann M., Cerwenka R. et al. (1986) Preliminary results of a randomized controlled study on the risk of hepatitis transmission of a two component fibrin sealant (TissucolTisseel) In: Schlag G. and Rehl H. (eds), FibrinSealant in Operative Medicine, vols l-7. Berlin: Springer, p. 51 Ellis D. A. and Pelausa E. 0. (1988) Fibrin glue in facial plastic and reconstructive surgery. 1, Ofolaryngol. 17, 74. Ellis D. A. and Shaikh A. (1990) The ideal tissue adhesive in facial plastic and reconstructive surgery. 1. Ofolayngol. 19, 68. Grey E. G. (1915) Fibrin as a haemostatic in cerebral surgery. Stlrg. Gynecol. Obsfet. 21, 452. Haymaker W. and Woodhall B. (1953) Periphal Newe Injuries. Philadelphia: W. B. Saunders. Hilfinhaus J. and Weidmann E. (1985) Fibrin glue safety: inactivation of potential viral contaminants by pasteurization of the human plasma components. Arzneimitfelforschung 11,1617. Journal Medical Association (1965) A guide to the evaluation of permanent impairment of the extremities. In: Joint Mofion: Method of Measuring and Recording (American Academy of Orthopedic Surgeons.) Edinburgh: Churchill Livingstone. Katzin H. M. (1945) Aqueous fibrin fixation of cornea1 transplants in rabbit. Arch. Ophthalrnol. 35, 415. Mahas H., Dinges H. I’., Lassman J. et al. (1972) Zur Nahtlosen Interfaszikularen Nerventransplantation in Tierexperiement. Wien. Med. Wochenschr. 122, 517.
Mathiowetz V., Kashmann N., Volland G. et al. (1985) Grip and pinch strength; normative data for adults. Arch. Phys. Med. Rehabil. 66, 69. Mathiowetz V., Wiemer D. and Federman S. M. (1986) Grip and pinch strength: norms for 6- to 19-year-olds. Am. J Occup. Ther. 40, 705. Panis R. and Scheele J. (1981) Hepatitisrisiko bei der Fibrineklebung in der HNO chirurgie. Layngol. Rhinol. Otol. 60, 367. Parry S. W. (1989) Reconstruction of the burned hand. Clin. Plusf. Surg. 16, 577. Parsky B. and House E. (1964) Review of Gross Anatomy. New York: Macmillan. Saltz R., Dimick A., Harris C. et al. (1989) Application of autologous fibrin glue in bum wounds. 1. Berm Cure Rehabil. 10, 504. Scheele J. and Schricker K. (1989) Hepatitisrisiko der Fibrineklebung in der Allgemeinchirurgie. Med. Welt. 32, 783. Sherif M. M. and Sato R. M. (1989) Severe thermal hand bums factors affecting prognosis. Berms 15, 42. Siedentop K. H., Harris D. M. and Sanchez B. (1985) Autologous fibrin tissue adhesive. Layngoscope 95, 1074. Siedentop K. H., Harris D. M., Sanchez B. et al. (1987) Autologous fibrin tissue adhesive biodegradation and systemic effects. Layngoscope 97, 1141. Stuart J. D., Morgan R. F., Kenney J. G. (1990) Single donor fibrin glue for hand bums. Ann. Plasf. Surg. 24, 524. Tidrick R. T. and Warner E. D. (1944) Fibrin fixation of skin transplants. Surgery 15, 90. Tisseel: Product Monograph (1985) Immuno (Canada) Limited, March. Vibe P. and Pless J. (1983) A new method of skin graft adhesion. Stand. 1. Phf. Reconsfr. Surg. 17,263. von Seelich T. and Red1 H. (1979) Das Fibrineklebesystem. Biochemische Grundlagen der Klebemethode. Dfsch. Z. MundKiefer-Gesichts-Chir. 3, 22s. Young J. Z. and Medawar E. D. (1944) Fibrin suture of peripheral nerves; measurement of the rate of generation. Lancef ii, 126. Paper accepted
2 January
1992.
Correspondence should be addressed to: Dr M. Vandevoort, castraat 29, 3580 Beringen, Belgium.
European Burn Association
5th European Burn Congress The Dome Centre, Brighton, England 20-23 September 1993 Further information from:
Dr Keith Jenkins MB ChB FCAnaes, Resident, EBA ‘93, McIndoe Bum Centre, Queen Victoria Hospital, East Grinstead, West Sussex RH19 3D2, England. Telephone: (0)342 410210. Fax: (0)342 317907.
Petrar-
(1992)
18, (5), 395-400
Printed in Great Britain
395
Fibrin glue in the treatment of dorsal hand burns W. Boeckx, M. Vandevoort, Ph. Blondeel, D. Van Raemdonck and E. Vandekerckhove Bum Centre, K. I-J. Louvain, Belgium
This paper analyses two groups of patients with only dorsal hand burns: groups I contains patients with a total of 15 burned hands ana’group I1 patients with 12 hand burns. The patients ingroup I were all treated by full sheet skin grafts using a two-component fibrin glue. Patients in group I1 undetwent Ihe traditional operative freatment without fibrin glue and the same postoperativephysical therapy programme. After follow-up periods of 6-11 months dgfoup I) and 12-21 months &oup II], we investigated in both groups, grip strength, key pinch, mobility, two-point discrimination and with the Semmes-Weinstein monofilaments. Our results prove &af after Ihe respective follow-up periods group I patients developed far better results for two-point discrimination, touch recognition and mobility.
History As early as 1915 successful experiments were reported by Grey (1915) with fibrin as a sealant and haemostatic agent for the control of haemorrhage in certain types of intracranial surgery. In 1940 Young and Medawar (1944) used it for peripheral nerve repair. In the mid-1940s Katzin (1945) reported the use of aqueous fibrin for the fixation of penetrating cornea1 grafts in rabbits. In 1943 Tidrick and Warner (1944) described a method for aiding the adhesive process in the grafting of skin. One year later, Cronkite et al. (1944) confirmed the technique - in which the skin transplant was immersed in a solution of titrated plasma, saturating the surface with fibrinogen, and then placing it on the recipient site after coating the tissue with a commercially prepared thrombin solution - as being superior, having extremely short binding time and achieving a solid mechanical bond. Furthermore the general healing process was speeded up by this technique. A JO-year hiatus then ensued while the idea lay dormant, probably because one factor limited the use of fibrin-based adhesions, namely the need to obtain fresh plasma from the recipient. In 1972 Mahas et al. introduced commercially prepared fibrin glue for peripheral nerve repair. From that time, fibrin glue has gained popularity as a biological adhesive among the surgical specialties, and has been reported to be a safe bioadhesive and sealant. Nowadays fibrin glue (Tissucol - Tisseel) is made from pooled human plasma obtained from licensed plasmapheresis centres in Central Europe. All donors are well known. They accept the need for clinical and biological follow-up. Donors are tested at every donation for HBS antigen using 0 1992 Butterworth-Heinemann 0305-4179/92/050395-06
Ltd
radioimmunoassay and for HIV antibody. To reduce the risk of non-A/non-B hepatitis transmission only plasma with alanine aminotransferase (ALT) levels below 25 U/litre are used for manufacturing fibrin sealant. Additionally thermoviro inactivation ensures a high degree of safety and avoids viral transmission. Currently the transmission of hepatitis B, hepatitis non-A/non-B and possibly AIDS has not been reported in the European literature. Alternatively the use of autologous fibrin tissue adhesive completely eliminates the danger of transmitting viral infections because component 1 (fibrinogen and aprotinin) is derived from the patient’s own blood (Panis and Scheele, 1981; Scheele and Schricker, 1981; Siedentop et al., 1985, 1987; Eder et al., 1986; Chakravorty and Sosnowski, 1989; Saltz et al., 1989; Stuart et al., 1990).
Physiology Fibrin glue, a biological product, mirrors the final common pathway of the normal coagulation cascade (von Seelich and Redl, 1979; Dresdale et al., 1985; Hilfinhaus and Weidmann, 1985; Tisseel, 1985; Ellis and Pelausa, 1988; Ellis and Shaikh, 1990). Fibrinogen, when combined with thrombin, develops loose monomeric fibrin. The presence of factor XIII (Grey, 1915) and calcium causes monomeric fibrin to polymerize lengthwise between the recipient and the skin graft forming a rapid and strong mechanical bond which results in the fibrin glue matrix. The normal degradation of this glue matrix by plasmin is blocked by aprotinin (Trasylol), an antiprotease, thus prolonging its sealant action (Fi’re I). The biochemical action of commercially prepared fibrin glue will result in sealing and bonding tissue and promoting haemostasis and wound healing. Thrombin Fibrinogen
LFibrin
Factor
XIII + Ca Fibrin
(monomer)
(polymer)
I Plasmin
-1
t Aprotinin I Fibrin
Figure 1. Schema showing fibrin.
the formation
degradation
and degradation
of
396
Bums (1992) Vol. IS/No.
5
160 ?? 140
12345678
9
10
11
12
13
14
15
Patients (no.) Figure 3. Key pinch: mean fibrin glue, 98.68 per cent; mean control, 92.99 per cent. 0.5 > P> 0.1. 1, Fibrin glue; 0, control. III 234567%
II
III 9
II 10 11
III 12 13
14
1 15
Patients (no.) Figure 2. Grip strength: mean fibrin glue, 84.45 per cent; mean control, 86.97 per cent. P> 0.5. ?? , Fibrin glue; 0, control.
?? ?? 0
0
?? ??
?? 2.5 0
2.0
0
w
??
??
0
i.5
0
?? ??
0
1.0
0
’
11
11
I
1 9
I 10
I 11
I 12
III 13 14
15
??
Patients (no.) Figure 5. Two-point discrimination on the dorsum of the fingers. Mean fibrin glue, 1.01 cm; mean control, 1.39 cm. 0.05 > P> 0.02. ?? , Fibrin glue; 0, control.
m
/
01
ot ! I 12345678
1
12345678
’
“1
11
9
1
10
’
11
11
12
13
11
14
15
Patients (no.) Figure 4. Two-point discrimination on the dorsum of the hand: mean fibrin glue, 1.33 cm; mean control, 2.18 cm. 0.01 > P> 0.001. H, Fibrin glue: 0, control.
Methods and operating technique The aim of this study was to provide clinical proof of firmer graft adhesion, better sensibility of the burned hand after grafting and a better functioning grafted hand with this technique using fibrin glue. For these reasons we used only the dorsal sites on burned hands. Surgery was performed on all patients within 1 week postbum. All patients required non-meshed split skin grafts of 0.010-0.012 in (0.25-0.28mm) taken by an electric dermatome. The recipient site was then stretched and denuded as much as possible with the electric dermatome and McGulian until a well-bleeding surface appeared. The most important bleeding spots were coagulated. The graft was cut to shape.for an accurate fit, followed by insertion of a few reinforcement sutures (vicryl4-0). Two separate solutions containing: (I) fibrinogen and aprotinin, and (2) thrombin and calcium, were mixed
(Tisseel, 1985; Cuny et al., 1986; Ellis and Pelausa, 1988), using a combined heating and stirring device (the fibri-
notherrn) to stir the components and maintain a temperature of 37°C. Once a viscous consistency was attained the fibrinogen concentrate and reconstituted thrombin were drawn in sterile syringes and locked in the duplojet dip. A common piston ensured equal volumes of fibrinogen and thrombin were mixed and ejected. Then, using the Tissumat pressure-regulator, the two-component tissue glue was sprayed on the recipient site as well as on the recipientcontact site of the graft which was already partially attached (see above). The graft was then placed in position and the remaining reinforcement sutures were inserted. On the fifth postoperative day the bandages were taken off. Only the successfully grafted hands were included in this study. Patients
During a 5-month period from December 1989 to April 1990 patients with a total of 15 dorsal hand bums (group I) were admitted to the bum unit of the St Pieter University Hospital, Louvain. The causes of these hand bums were: thermal (86.6 per cent), and electrical (13.3 per cent). The patient’s age distribution ranged from 8 to 40 years (mean of 31 years). The average TBSA bum was 15 per cent. Patients in this first group were all treated using ,the two-component tissue glue. A control group (group II) of patients with a total of 12 dorsal hand bums had been admitted in our hospital during
Boeckx et al.: Fibrin glue in treatment of dorsal hand bums
I
I
2.83
3.61
4.31
397
mJ
2.83
3.61
4.31
4.56
6.65
6.65
Log force
Log force Figure 6. Semmes-Weinstein monofilaments on the dorsal surface of the hand. Mean fibrin glue, 3.83 log force; mean control, 4.41 log force. 0.5 > P> 0.1. ?? , Fibrin glue; 0, control.
Figure 7. Semmes-Weinstein monofilaments on the dorsal surface of the fingers. Mean fibrin glue, 3.35 log force; mean control, 4.08 log force. 0.5 > P> 0.1. ?? , Fibrin glue; @, control.
the previous 9 months, March 1989 to November 1989. In this group all the patients sustained thermal bums with an average TBSA bum of 16 per cent. The patients’ ages ranged from 26 to 57 years with a mean of 35 years. The patients’ hands were all treated with non-meshed split skin grafts of 0.012-0.012 in. (0.25-0.28 mm) taken by an electric dermatome. In both study groups only successfully grafted hands were included. None of the patients included in this study had neurological problems, either before or after the bum accident. The only difference between the patients in the control group and in the test group was the use of the two-component tissue glue to spray on the recipient site and on the recipient-contact site of the graft of the test group patients. All other methods of treatment were identical.
the same type of splinting technique. All patients were fitted with a custom-made pressure glove after the hand had stabilized.
Management
In all patients the bums were diagnosed as deep partial or full skin thickness, and were not expected to heal without surgical intervention (Parry, 1989; Sherif and Sato, 1989). The operation was carried out between 3 and 5 days after burning. Physiotherapy, using the same rehabilitation programme in all patients, started on the day of admission and was carried out in both groups by the same physiotherapist. On day 5 post operation active range of motion (ROM) exercises were begun. Active assisted exercises (with progressively increasing intensity) were started on the day of admission and day 5 postoperation. Splinting of the hand was performed on the day of admission and again during each night from day 5 postoperation in both groups with
Figure 8. Clinical result of a fibrin glue treated hand after 5 days; a perfect take of the graft with only a few bleeding spots left.
Results The follow-up period ranged from 6 to 11 months in the fibrin glue group and from 12 to 21 months in the control group. After these periods all the patients underwent tests to investigate strength, sensibility and mobility. Strength
Grip strength and key pinch were measured. Each of the tests used the methods described by Agnew and Maas (1982) and Mathiowetz et al. (1985, 1986). The patients’ performances were then compared to the average clinical norms related to sex and age (Mathiowetz et al., 1985,1986) and expressed as percentages of the mean values. Figure2 shows that no significant differences were found between the two groups of patients, although even the data for the traditional grafting technique (control group) showed better results (mean 87.0 per cent) than the technique using fibrin glue (mean 84.4 per cent). Probably this is due to the longer follow-up period of the patients in the control group. However, the results for key pinch (Figure 3) show a slight difference between the two grafting techniques significant at the 0.5 > P > 0.1 level. The data for the hands grafted using the fibrin glue technique (mean 98.7 per cent) show that key pinch recuperation was stronger and much faster than that of
Figure9. Clinical result of a fibrin glue treated hand after 6 months showing a complete recovery of mobility and good aesthetic result.
Bums (1992)Vol. 18/No. 5
398
the group treated by the traditional technique (mean 93.0 per cent). Over 11 months the patients in the fibrin glue group improved with almost complete restoration of key pinch. This is in contrast with the follow-up period of 12-21 months in the control group. In both groups we observed that the general results for the key pinch test accord better with the average clinical norms than the data for the test measuring grip strength. This phenomenon can be explained by the fact that key pinch is a test which involves the use of a much smaller muscle group than that for the grip strength test. Also the hand movement, and thus the skin movement, during which strength is exercised, is a lot easier with the key pinch test. Additionally the key pinch is more important for carrying out normal hand function, certainly as far as delicate movements are concerned. Sensibility The sensibility of the grafted hands was tested using two tests: a two-point discrimination and a test with the Semmes-Weinstein monofilaments (Haymaker and Woodhall, 1953; Parsky and House, 1964; Bell, 1984; Bell and Tomancik, 1987). We applied the five filaments that best represented changes in functional levels of touch recognition. The dorsum of the hand and fingers was examined separately. Significant differences were noticed for twopoint discrimination between the two groups of treated hands. On the dorsum of the hand the differences were even significant at the 0.01> P> 0.001 level with a mean value of 1.33 cm for the fibrin glue-treated hands and 2.10 cm for the hands that received a traditional treatment without fibrin glue (Figure4). Significant differences in two-point discrimination on the dorsum of the fingers between the two groups of treated hands were observed (0.05 > P> 0.02). Far better data in the fibrin glue group (mean 1.01cm) were found compared with the control group (mean 1.39 cm) (Figtlre5). Although there are quite important differences between the two groups, the overall data for the hands treated by fibrin glue are still only fair and even poor in comparison with the values for normal hands according to the American Society for Surgery of the Hand. Two-point < 0.6 cm; discrimination: good, fair, 0.6-1.0 cm; poor, 1.1-1.5 cm. The Semmes-Weinstein monofilaments also give a good idea of the post-traumatic recuperation of the burned hand, especially where touch recognition is concerned. This assesses the two-point discrimination as the amount of tactile stimulus which can be distinguished per square centimetre. The test with the Semmes-Weinstein monofilaments indicates a statistically significant difference in touch recognition between the two groups of treated hands. This touch recognition is expressed in terms of force or log force which needs to be exerted on the skin of the investigated area (Table I). The normal values for the dorsal surfaces of the
hands and fingers are about 2.83 log force. In our studies the fibrin glue-treated hands required a mean of 3.83 log force on the dorsal surface of the hand and 3.35 log force on the dorsal surface of the fingers. The data for the hands treated traditionally had a mean of 4.41 log force on the hand surface and 4.08 log force on the finger surface. These differences between the two groups are both statistically significantly at the 0.5 > I’> 0.1 level(Figttres6, 7) Thus there is a significantly better recovery of sensibility after bums when fibrin glue is used in the operating technique. Mobility Our study also reviewed the mobility of hands with dorsal bums starting from 0” to the utmost flexion. Measurements were made successively with wrist flexion, flexion of the metacarpophalangeal joint (MCP), the proximal interphalangeal joint (PIP) and the distal interphalangeal joint (DIP). For references we used data on hand flexion derived from the four studies shown in TubleII. FigureIOshows the flexion of the fibrin glue-treated hands compared with the mobility of the hands treated traditionally. All numbers marked out in the diagrams are the mean values of the observed data respectively in the two groups of patients. So far as wrist flexion is concerned there was little difference between the two mean values (mean fibrin glue group 70.60” and mean group II 67.83” with 0.5 > P> 0.1). These results reflect our selection of bums affecting only the dorsal surfaces of the hands and fingers. The most marked mean differences are found in the flexion of the MCP joints of all five fingers. The MCP joint is situated on all hands between two burned and therefore treated surfaces. We conclude therefore that the MCP joint is the most important joint to measure the recovery of flexion after bums. This joint showed significant differences at the 0.5 > P> 0.1 level for digit 1, at the 0.1> P> 0.05 level for digit 2, and even at the 0.05 > P> 0.02 level for digits 3,4 and 5. Differences in flexion of the PIP joints are also fairly good and significant: 0.5 > P> 0.1for digits 2 and 3,0.1> P> 0.05 for digit 4 and 0.05> P> 0.02for digit 5. It is striking that between the two groups the difference in flexion of the MCP and PIP joints in digits 3, 4 and 5 is of a greater significance than in digits I and 2. The results for the interphalangeal joint (IP) of digit 1 and the DIP joints of the other four fingers indicate that the more distal the place of the hand bum, the less significant the difference in flexion, findings which probably reflect the fact that the more distal areas of the finger were subject to more minor bums which healed spontaneously in many patients
(Figures8, 9).
Table II References
Table1 Force (9)
0.080 0.217
2.35 4.19 279.4
Log force
2.83 3.61 4.31 4.56 6.65
Wrist flexion MCP PIP DIP
1
2
70” 90 100 70
70 90 100 70”
??
3
4
Mean
90
80 90 100 90
73” 90 100’ 80”
“Journal Medical Association, 1958. Xommittee of California Medical Association, %lark, 1920. ‘The Committee on Joint Motion, 1965.
1960.
Boeckx et al.: Fibrin glue in treatment of dorsal hand burns
MCP:
1
Digit
,j
399
mean fibrin glue 86.66’ mean control 77.08’ 0.5>P > 0.1
\ I,
)
IP:
yea;
DIP:
‘,‘,“,~:,g’,upl$.““”
P > 0.5
/’
Wrist
flexion:
mean fibrin glue mean control 79.91° 0.5 > P> 0.1
\
mean fibrin glue 70.60’ mean control 67.83’ 0.5 > P > 0.1
mean fibrin glue 90.00” mean control 83.75O 0.05 >P > 0.02 Wrist mean
DIP:
mean fibrin glue 80.66’ mean control 78.33’ 0.05 > P > 0.02
flexion: fibrin glue
mean fibrin glue 98.86’ mean control 92.91° 0.5 > P > 0.01
\
\
\
Wrist
\
MCP:
IP:
PIP: 70.60’
mean fibrin glue 89.40° mean control 84.580 0.1 >P > 0.05
mean fibrin glue 98.33’ mean control 93.75O 0.5> P > 0.1
Wrist
DIP: mean fibrin glue 79.86O mean control 78.33’ 0.5 >P > 0.1
d PIP:
Figure 10.
MCP: mean fibrin
glue 90.33O mean control 83.33O 0.05 > P > 0.02
flexion: PIP:
DIP: mean fibrin glue 79.66’ mean control 79.16O / P > 0.5
flexion:
mean fibrin glue 98.33O mean control 93.33’ 0.05 0.1 > P>
\ \ \
MCP: \
/
/
mean fibrin glue 89.66’ mean control 82.50° 00.5> P > 0.02
/
mean fiGin glue 99.40’ mean control 93.33O 0.05 ? P > 0.02
Diagrams
on mobility.
-,
Fibrin
glue; ----,
Discussion In a previous study (Vibe and Pless, 1983) it was suggested that on recipient sites where grafts are subjected to stress movements shortly after placement of the graft survival improved substantially when fibrin glue was used during the operating technique. Our study also indicates that functional recovery after bums is much improved in terms of sensibility, mobility and strength and also the time to reach a certain value of function is increased. This is quite clear when we consider the differences in follow-up period between group I (6-11 months) and group II (12-21 months). Our study also indicated that the use of fibrin glue during the operation is of little benefit for gaining strength after a bum accident. The regaining of strength is more dependent on the time after the bum than on operating technique because muscle tissue is more responsible for exercising strength than epidermis and dermis. A rapid and good healing of the burned skin areas is of great importance for the recuperation of sensibility and mobility. First of all because perception of tactile stimuli depends on the condition of the epidermis and dermis where free sensory nerve endings are abundant and penetrate into the granular layer. Secondly, joint articulation
control.
and muscle working has a less significant effect on mobility than skin elasticity. Therefore the condition of the skin graft, the percentage ‘take’ of the graft and the recovery of elasticity after grafting are extremely important. The operating technique using fibrin glue is faster than the traditional way because only a minimal number of reinforcement sutures are required to fix the graft on the recipient site. In almost all patients it is even possible to work without suture points, it goes without saying however that the importance of good applied bandages cannot be overestimated.
References Agnew P. J. and Maas F. (1982) Hand function related to age and sex. Arch. Phys. Med. Rehabil. 63, 269. Bell J. A. (1984) Semmes-Weinstein monofilaments testing for determining cutaneous light touch/deep pressure sensation. % Star, 44, (2). Bell J. A. and Tomancik L. (1987) The reliability of the SemmesWeinstein monofilaments. 1. Hand Surg. IZA, 155.
400
Bums(1992)Vol.m/No.5
Chakravorty R. C. and Sosnowski K. M. (1989) Autologous fibrin glue in full thickness skin grafting. Ann. Plasf. Surg. 26, 488. Clark W. A. (1920) A system of Joint Movements. 1. Orfhop. Surg. 2, 12. Committee of California Medical Association. The Industrial Accident Committee of the State of California (1960) Evaluation of lndwfriul Disability. Oxford: Oxford University Press. The Committee on Joint Motion (1965) Joint Motion: Method of Measuring and Recording (American Academy of Orthopedic Surgeons.) Edinburgh: Churchill Livingstone. Cronkite E. P., Lozer E. L. and Deaver J. M. (1944)Use of thrombin and fibrinogen in skin grafting. JAMA 124,976. Curry J.-F., Schmutz J.-L., Huber G. et al. (1986) Tissucol et Transglutine: amelioration dans la pratique des greffes cutanees. Ann. Dermufol. Venereal. 113, 739. Dresdale A., Bowman F. O., Malm J. R. et al. (1985) Haemostatic effectiveness of fibrin glue derived from single donor fresh frozen plasma. Ann. I’boruc. Surg. 40,385. Eder G., Neumann M., Cerwenka R. et al. (1986) Preliminary results of a randomized controlled study on the risk of hepatitis transmission of a two component fibrin sealant (TissucolTisseel) In: Schlag G. and Rehl H. (eds), FibrinSealant in Operative Medicine, vols l-7. Berlin: Springer, p. 51 Ellis D. A. and Pelausa E. 0. (1988) Fibrin glue in facial plastic and reconstructive surgery. 1, Ofolaryngol. 17, 74. Ellis D. A. and Shaikh A. (1990) The ideal tissue adhesive in facial plastic and reconstructive surgery. 1. Ofolayngol. 19, 68. Grey E. G. (1915) Fibrin as a haemostatic in cerebral surgery. Stlrg. Gynecol. Obsfet. 21, 452. Haymaker W. and Woodhall B. (1953) Periphal Newe Injuries. Philadelphia: W. B. Saunders. Hilfinhaus J. and Weidmann E. (1985) Fibrin glue safety: inactivation of potential viral contaminants by pasteurization of the human plasma components. Arzneimitfelforschung 11,1617. Journal Medical Association (1965) A guide to the evaluation of permanent impairment of the extremities. In: Joint Mofion: Method of Measuring and Recording (American Academy of Orthopedic Surgeons.) Edinburgh: Churchill Livingstone. Katzin H. M. (1945) Aqueous fibrin fixation of cornea1 transplants in rabbit. Arch. Ophthalrnol. 35, 415. Mahas H., Dinges H. I’., Lassman J. et al. (1972) Zur Nahtlosen Interfaszikularen Nerventransplantation in Tierexperiement. Wien. Med. Wochenschr. 122, 517.
Mathiowetz V., Kashmann N., Volland G. et al. (1985) Grip and pinch strength; normative data for adults. Arch. Phys. Med. Rehabil. 66, 69. Mathiowetz V., Wiemer D. and Federman S. M. (1986) Grip and pinch strength: norms for 6- to 19-year-olds. Am. J Occup. Ther. 40, 705. Panis R. and Scheele J. (1981) Hepatitisrisiko bei der Fibrineklebung in der HNO chirurgie. Layngol. Rhinol. Otol. 60, 367. Parry S. W. (1989) Reconstruction of the burned hand. Clin. Plusf. Surg. 16, 577. Parsky B. and House E. (1964) Review of Gross Anatomy. New York: Macmillan. Saltz R., Dimick A., Harris C. et al. (1989) Application of autologous fibrin glue in bum wounds. 1. Berm Cure Rehabil. 10, 504. Scheele J. and Schricker K. (1989) Hepatitisrisiko der Fibrineklebung in der Allgemeinchirurgie. Med. Welt. 32, 783. Sherif M. M. and Sato R. M. (1989) Severe thermal hand bums factors affecting prognosis. Berms 15, 42. Siedentop K. H., Harris D. M. and Sanchez B. (1985) Autologous fibrin tissue adhesive. Layngoscope 95, 1074. Siedentop K. H., Harris D. M., Sanchez B. et al. (1987) Autologous fibrin tissue adhesive biodegradation and systemic effects. Layngoscope 97, 1141. Stuart J. D., Morgan R. F., Kenney J. G. (1990) Single donor fibrin glue for hand bums. Ann. Plasf. Surg. 24, 524. Tidrick R. T. and Warner E. D. (1944) Fibrin fixation of skin transplants. Surgery 15, 90. Tisseel: Product Monograph (1985) Immuno (Canada) Limited, March. Vibe P. and Pless J. (1983) A new method of skin graft adhesion. Stand. 1. Phf. Reconsfr. Surg. 17,263. von Seelich T. and Red1 H. (1979) Das Fibrineklebesystem. Biochemische Grundlagen der Klebemethode. Dfsch. Z. MundKiefer-Gesichts-Chir. 3, 22s. Young J. Z. and Medawar E. D. (1944) Fibrin suture of peripheral nerves; measurement of the rate of generation. Lancef ii, 126. Paper accepted
2 January
1992.
Correspondence should be addressed to: Dr M. Vandevoort, castraat 29, 3580 Beringen, Belgium.
European Burn Association
5th European Burn Congress The Dome Centre, Brighton, England 20-23 September 1993 Further information from:
Dr Keith Jenkins MB ChB FCAnaes, Resident, EBA ‘93, McIndoe Bum Centre, Queen Victoria Hospital, East Grinstead, West Sussex RH19 3D2, England. Telephone: (0)342 410210. Fax: (0)342 317907.
Petrar-
