A Prospective Study of 100 Gelatin-Sealed Aortic Grafts D.B. Reid, FRCS, J.G. Pollock, FRCS, Glasgow, Scotland
A gelatin-sealed knitted Dacron graft has been developed which has zero porosity at implantation and does not require preclotting. Its patency rate up to 57 months and effectiveness at saving blood loss have been studied. Gelatin-sealed aortic grafts were implanted into 100 consecutive patients--77 men, 23 women. Surgery was performed for aneurysm in 36 patients (including four with rupture), intermittent claudication in 44, rest pain in 17, and gangrene in three, over an 18 month period. The patients were followed up prospectively for 57 months. Perioperative mortality was 1%. Cumulative primary graft patency was 99%. There was no measurable blood loss at implantation. Forty-seven patients required blood transfusion: mean volume transfused was 430 ml. There were no problems related to the sealant. (Ann Vasc Surg 1991 ;5:320-324). KEY WORDS:
Grafts; gelatin-sealed aortic grafts; aortic implantation.
The introduction of sealed, knitted Dacron grafts has enabled the vascular surgeon to implant a knitted material which imparts zero porosity at implantation, saving time and minimizing blood loss. While this type of graft is attractive to the surgeon the most important clinical end point for the patient is graft patency. Dacron has become the material of choice in the high flow situation in wide bore vessels [1]. Knitted Dacron has superior handling characteristics compared to the more rigid and likely to fray woven Dacron, and it is better incorporated by the host tissues [2]. These two qualities of knitted Dacron are due to its high porosity which previously required a preclotting stage before insertion to render the graft impervious to blood. In the past a woven Dacron graft was preferred to a graft of knitted construction in resection of aortic aneurysm. This is because the size of the graft cannot be determined until the neck of the aneuFrom the Unitfor Peripheral Vascular Surgery, Glasgow Royal Infirmary, Glasgow, Scotland. Reprint requests: Mr. John G. Pollock, Unitfor Peripheral Vascular Surgery, Glasgow Royal Infirmary, Glasgow, Scotland.
rysm is dissected and intravenous heparin has been given [3]. Heparinization makes preclotting of the appropriate knitted graft impossible. A sealed graft overcomes this problem, allowing a graft of knitted construction to be used. A sealed graft that saves blood and hence transfusion is particularly important at a time when blood transfusion itself may be potentially harmful. These potential benefits of a sealed graft have been examined in this study together with the more important clinical end point of graft patency. Our clinical experience with more than 700 gelatinsealed implants is focused into a prospective study of the initial 100 patients undergoing aortic surgery in the Unit for Peripheral Vascular Surgery, Glasgow Royal Infirmary.
MATERIALS AND METHODS Gelseal aortic grafts* were implanted into 100 consecutive patients, 77 men, 23 women. The patients' mean age was 64 years (range 41-80). Their risk factors are shown in Table I. Fifty-one patients * Vascutek, Ltd., Inchinninan, Renfrewshire, Scotland.
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TABLE I.mNumber of patients with risk factors Cardiac history Hypertension Cerebral incident Family history of peripheral arterial disease Diabetes
31 18 10 9 5
were smokers immediately prior to surgery, another 46 patients were ex-smokers of greater than one month duration, and only three patients had never smoked before. Surgery was performed for aneurysm in 36 patients (including four with rupture), intermittent claudication in 44, rest pain in 17 and gangrene in three over a period of 18 months (August 1985 to February 1987). All surgery was carried out with prophylactic antibiotics using intravenous third generation cephalosporins at induction of anesthesia with two further doses over 24 hours. Systemic heparin (5,000 IU) was given prior to aortic crossclamping. This was reversed by protamine in a titrated dose. Intravenous volume loading was carried out by the anesthetist before declamping. The most common size of aortic graft was 16 x 8 mm (range 14 x 7 mm to 22 x 11 mm). Ninety-six aortic bifurcation grafts and four aortic tube grafts were inserted. The proximal anastomosis was end-to-side in 38 cases, end-to-end in 31, and the inlay technique for aneurysm performed in 31. Thirty-eight iliac and 153 femoral anastomoses were performed. There was one patient in whom only one distal anastomosis was performed because of the severity of arterial disease in the other limb with no adequate runoff. Operative lumbar sympathectomy was carried out concurrently in 36 patients, and five patients had extension grafts. There were two femoropopliteal bypass grafts, one bilateral femoropopliteal bypass, one tube extension from the lower limb of the aortic graft to the superficial femoral artery, and one extension graft from the lower limb of the graft to the profunda femoris artery. Four concurrent cholecystectomies were performed, and two cases also required reimplantation of the inferior mesenteric artery. Blood loss at surgery was monitored together with the need for blood transfusion and quantity transfused. The decision to transfuse blood was the anesthetist's. Blood transfusion was prescribed when blood loss at operation exceeded 750 ml and on clinical grounds in some patients when blood loss was less than 750 ml. An early complication was defined as occurring at less than 30 days from implantation and a late complication at more than 30 days. The patients were followed up prospectively and patency was assessed annually. The cohort was reviewed as a whole each year. Graft patency was
321
assessed clinically by palpation of pulses, and objectively by preoperative and postoperative ankle/ brachial pressure index (ABPI) and Doppler waveform analysis. All patients had postoperative ABPI and Doppler waveform analysis over the distal limbs of aortic bifurcation grafts. Four patients with aortic tube grafts were assessed without Doppler waveform analysis over the distal limbs of aortic bifurcation grafts. Four patients with aortic tube grafts were assessed without Doppler waveform analysis; all had normal peripheral pulses and normal ABPI. Where there was any doubt about patency, following clinical examination, ABPI, and Doppler waveform analysis, aortography was performed. This was only performed on four patients who had Doppler waveforms which were technically difficult to obtain. (This is in accordance with the standards and definitions described by the Ad Hoc Committee on Reporting Standards, Society for Vascular Surgery/North American Chapter, International Society for Cardiovascular Surgery [4]).
RESULTS Primary cumulative graft patency is 99% at 57 months follow-up. One limb of an aortic graft occluded at 15 months (Table II, Fig. 1). Perioperative mortality was 1%. One patient suffered a cerebrovascular accident 16 days after surgery and died. There was no measurable blood loss at implantation from the body of the sealed graft. The mean blood loss for each patient group is shown in Table III. The percentage of patients requiring blood transfusion for aneurysmal and occlusive disease is shown in Figure 2. Fifty-three patients did not require blood transfusion. Only 61% of patients with aneurysmal disease required blood transfusion and only 39% of patients with occlusive disease. During subsequent follow-up 12 deaths occurred. The causes of death are shown in Table IV. The commonest cause of death was myocardial infarction. All grafts were known to be patent immediately before death. Early complications
One patient developed lower limb ischemia immediately postoperatively. A popliteal embolectomy successfully retrieved atheromatous debris. Another patient occluded one limb of his graft immediately postoperatively, again embolic atheromatous "trash" material was successfully removed. One limb of a graft occluded eight days after implantation. At exploration a dissected intimal flap was repaired in the profunda femoris artery. These three cases were technical complica-
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PROSPECTIVE STUD Y OF GELATIN-SEALED GRAFTS
322
TABLE II.--Life table analysis No. withdrawn due to: Loss Death
Interval patency rate
Cumulative patency (%)
Standard error (%)
Interval (months)
No. at risk
No. failed
0-1
100
0
0
0
1.00
100
1-3
98
0
0
2
1.00
100
0
3-6 6-9 9-12
98 97 97
0 0 0
0 0 0
0 1 0
1.00 1.00 1.00
100 100 100
0 0 0
12-15
96
0
0
1
1.00
100
0
15-18 18-24 21-24 24-27 27-30 30-33 33-36 36-39 39-42 42-45 45-48 48-51 51-54 54-57
94 94 94 93 91 90 90 72 48 38 29 16 6 2
1 0 0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 0 0 0
1 0 0 0 2 1 0 2 2 0 0 0 0 0
0.99 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00
99 99 99 99 99 99 99 99 99 99 99 99 99 99
tions of the surgery and not related to the sealed graft. Another patient undergoing emergency revisional surgery for an occluded, nonsealed aortic graft inserted three years previously and who also had two thrombectomy procedures to a femoropopliteal extension graft one year previously, required a mid-thigh amputation. At insertion of the new sealed aortic graft the profunda femoris artery was too diseased to accept a limb of the graft. There were 10 patients with postoperative chest infection, two superficial groin wound infections, five patients who developed heart failure, one myocardial infarction and one pulmonary embolism. Two patients developed Legionnaires' disease immediately postoperatively (there was a point source outbreak of Legionnaires' disease in the hospital at this time involving 16 patients) [5]. Both of these two patients recovered; one patient developed a desquamation skin rash which was believed to be due to the antibiotics given for Legionnaires' disease.
0
1.02 1.02 1.02 1.02 1.02 1.04 1.04 1.04 1.06 1.06 1.06 1.06 1.06 1.06
anastomosed to the external iliac artery, and there was progression of arterial disease in the common femoral artery. This one occluded limb was successfully revised by a crossover graft from the patent limb of the aortic graft to the opposite profunda femoris artery with a short jump graft to the superficial femoral artery. Two patients developed ischemia due to progression of distal disease in the period of follow-up. One had recurrent ischemic rest pain two years after his aortic biprofunda graft. A femoropopliteal extension was performed, the sealed aortic graft was noted to be patent at operation. The femoropopliteal extension corrected a stenosis at the distal anastomosis. Both grafts continue to function and he no longer has rest pain. The other patient, who was diabetic, developed digital ischemic ulceration one year after an aortobifemoral graft. No further reconstructive surgery was possible as he had 100' 1 limb occluded at 15 months Number of
Late complications
One graft limb occluded at 15 months. At revisional surgery the occluded distal limb had been
aortic grafts at risk 50.
TABLE III.mMean blood loss for patient groups Mean Mean Total blood volume No. of no. Reason for loss (ml) patients of surgery (ml) transfused transfused patients Aneurysm Gangrene Rest pain Claudication
1170 850 792 771
770 650 450 440
22 2 7 16
36 3 17 44
0
0
12
24
36
48
Months
Fig. 1. Patency rate of aortic grafts with time.
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TABLE IV.--Cause of death
Month postoperative 2 9 14 17 26 27 28 31 36 38 40 41
Cause of death Ischemic heart disease Carcinoma of bladder Carcinoma of pancreas Carcinoma of liver Diverticular peritonitis Myocardial infarction Myocardial infarction Congestive cardiac failure Renal failure Chronic obstructive airways disease Cerebrovascular disease Myocardial infarction
m
Occlusive
Aneurysmal
Fig. 2. Percentage of patients requiring blood transfusion with aneurysm or occlusive disease,
patent superficial femoral and popliteal arteries. A digital amputation has been successful and this patient is currently well. One further patient complained of persistent groin discomfort, another has complained of impotence.
DISCUSSION This is a study of the first 100 patients who had gelatin-sealed aortic grafts implanted in Glasgow Royal Infirmary. The performance of this graft has been assessed in routine clinical practice with regard to the long-term patency and blood loss. This study is not randomized to compare unsealed grafts. Many such series of preclotted Dacron exist. By choosing 100 consecutive patients the authors believe that this was a realistic challenge to the graft when assessing patency and blood loss (the series includes 36 abdominal aortic aneurysms, four of which were ruptured and one inflammatory; 17 patients who had ischemic rest pain; and three with gangrene). The 99% cumulative patency rate at 57 months compares favorably with other series, however the authors do not claim that it is significantly
better than preclotted Dacron or polytetrafluoroethylene (PTFE) series since this present study was not randomized (Table V) [6-12]. Gelatin has been used safely for many years as a plasma expander [13]. The use of gelatin as a sealant allows the graft to be impervious to blood at implantation, and, being biodegradable, it may be removed within 14 days [14]. The rate of gelatin removal can be altered because of the nature of gelatin chemistry: reduction in cross-linkage is achieved by decreasing the number of available amino groups prior to exposure to formaldehyde. The reduction in cross-linkage speeds up its biodegradation, and the sealant also exhibits a relatively low thrombogenicity [15]. In vitro studies have assessed the safety of the gelatin-sealed graft treated by formaldehyde. They have shown the grafts to be nontoxic and nonmutagenic [2]. A major advantage of knitted grafts is their excellent healing properties, i.e., incorporation of the graft by the host. Granulation tissue in the form of fibroblasts and capillary buds penetrate the fabric within weeks, with knitted material being more porous than woven. This anchors the pseudointima and the prosthesis to the tissues. The gelatin-sealed graft is constructed with a low internal and high external velour. This enables the development of a thin, firm pseudointima and also rapid tissue ingrowth and incorporation [15]. This concept has been confirmed by another study: a
TABLE V.--Patency for aortic surgery Author Chang [6] Brewster [7] Petrovic [8] Karner [9] Cintora [10] Nevelsteen [11]
Year 1981 1978 1989 1988 1988 1980
Material Dacron Dacron PTFE PTFE/Dacron PTFE/Dacron Dacron
Vanttinen [12]
1975
Dacron
PTFE
-
Polytetrafluoroethylene
No. of patients 188 261 132 60/52 170/142 352 177
Years follow-up 6 5 4 2 4 5 10 5
Patency rate (%) 84 91 98.4 97/95 97/90 80 62 91
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PROSPECTIVE STUD Y OF GELATIN-SEALED GRAFTS
high internal velour has been shown to produce a thick pseudointima [16]. The lack of inflammatory response to the sealant and its inherently low thrombogenicity may be important factors in long-term patency. In this context, we performed clinical studies measuring C-reactive protein and alpha-l-acid glycoprotein, and we have shown that gelatin-sealed grafts do not exaggerate the inflammatory response [17]. In vitro and clinical thrombogenicity studies assessed the gelatin-sealed Dacron compared to identical but untreated standard knitted Dacron. Gelatin-sealed grafts had significantly fewer platelets adhering when examined under the scanning electron microscope, suggesting that the gelatin-sealed graft has a lower thrombogenicity [18,19]. However the gelatin sealant is unlikely to contribute to long-term graft patency since it is rapidly removed by biodegradation. The 99% cumulative patency rate may reflect the graft skeleton and the consultancy-oriented practice of the unit.
CONCLUSIONS This prospective study showed a 99% cumulative patency rate at nearly five years follow-up (57 months). The sealed graft saves time and blood loss, important at a time when blood transfusion may be harmful. There was no problem related to the gelatin sealant. The gelatin-sealed graft has advantages over non-sealed Dacron. Its handling characteristics make it easy to use not only in the aortofemoral region, but we have obtained favorable results in above-knee femoropopliteal and axillofemoral regions where it can be tunnelled for distance, impervious to blood.
REFERENCES I, COOLEY DA. Development of vascular prosthesis to meet the surgeons requirements. In: GREENHALGH RM (ed). Diagnosis Techniques and Assessment Procedures in Vascular Surgery. London: Grune and Stratton, 1985, pp 493-502. 2. POLLOCK JG, DRURY JK, CUSCHIERI RJ, et al. New knitted Dacron prosthesis---experimental and clinical resuits. Rev Angiol Chir Vasc 1986;16:113-121.
mmm
ANNALS OF VASCULAR SURGERY
3. REID W, POLLOCK JG. A Surgeons Management of Gangrene. London: Pitman Medical, 1978. 4. RUTHERFORD RB, et al. Suggested standards for reports dealing with lower extremity ischemia. J Vasc Surg 1986;4: 80-94. 5. TIMBURY MC, DONALDSON JR, MC CARTNEY AC, et al. Outbreak of Legionnaires disease in Glasgow Royal Infirmary: microbiological aspects. J Hyg (Lond) 1986;97: 393-403. 6. CHANG JB. Surgical treatment of aorto-iliac artery disease. Angio 1981 ;32:73-105. 7. BREWSTER DC, DARLING RC. Optimal methods of aortoiliac reconstruction. Surgery 1978;84:739-748. 8. PETROVIC P, LOTINA S, DJORDJEVIC M, et al. Results of 132 PTFE (Gore-tex) bifurcated graft implantations. J Cardiovasc Surg 1989;30:897-901. 9. KARNER J, SCHEMPER M, TELEKY B, et al. Aorto-ybifurcation grafts: Dacron versus PTFE. Preliminary results of a randomized prospective study. Int Surg 1988;73:218220. I0. CINTORA I, PEARCE DE, CANNON JA. A clinical survey of aortobifemoral bypass using two inherently different graft types. Ann Surg 1988;208:625-630. 11. NEVELSTEEN A, SUY R, DAENEN A, et al. Aortofemoral grafting: factors influencing late results. Surgery 1980; 88:642-653. 12. VANTTINEN E, INBERG MV. Aorto-ilicofemoral arterial reconstructive surgery. Acta Chir Scand 1975;141:600-608. 13. LUNDSGAARD-HANSEN P, TSCHIRREN B. Clinical experience with 1200 units of modified fluid gelatin. Joint WHO/1985 Symposium on Standardization of Albumin and Plasma Substitutes, Geneva, 1986. Develop Biol Stand 4F Basel: S. Karger, 1981, pp 251-256. 14. GUIDOIN RJ, MARCEAU D, RAO TJ, et al. In vitro and in vivo characterization of an impervious polyester arterial prosthesis: the Gelseal triaxial graft. Biomaterials 1987;8: 433-441. 15. REID DB, POLLOCK JG. The gelatin pre-coated prosthesis. II Congresso Internazionalle Sulle Protesi Vascolari. Monduzzi Editore, 1989, pp 83-90. 16. WU H, ZAMMIT H, SAUVAGE LR, et al. The influence of inner wall filamentousness on the performance of small and large caliber arterial grafts. J Vasc Surg 1985;2:255-262. 17. VOHRA R, DRURY JK, SHAPIRO D, et al. Sealed versus unsealed Dacron prosthesis: a comparison of the acute phase protein response. Ann Vasc Surg 1987;1:548-551. 18. DRURY JK, ASHTON TR, CUNNINGHAM JD, et al. Experimental and clinical experience with a gelatin impregnated Dacron prosthesis. Ann Vasc Surg 1987;1:541-547. 19. ZAHRANI HA, CUSCHERI RJ, LOWE GDO, et al. Monoclonal antibody enzyme immunoassay in the study of thrombogenicity of preclotted and gelatin impregnated aortic prosthesis. Ann Vasc Surg 1989;4:248-250.
A gelatin-sealed knitted Dacron graft has been developed which has zero porosity at implantation and does not require preclotting. Its patency rate up to 57 months and effectiveness at saving blood loss have been studied. Gelatin-sealed aortic grafts were implanted into 100 consecutive patients--77 men, 23 women. Surgery was performed for aneurysm in 36 patients (including four with rupture), intermittent claudication in 44, rest pain in 17, and gangrene in three, over an 18 month period. The patients were followed up prospectively for 57 months. Perioperative mortality was 1%. Cumulative primary graft patency was 99%. There was no measurable blood loss at implantation. Forty-seven patients required blood transfusion: mean volume transfused was 430 ml. There were no problems related to the sealant. (Ann Vasc Surg 1991 ;5:320-324). KEY WORDS:
Grafts; gelatin-sealed aortic grafts; aortic implantation.
The introduction of sealed, knitted Dacron grafts has enabled the vascular surgeon to implant a knitted material which imparts zero porosity at implantation, saving time and minimizing blood loss. While this type of graft is attractive to the surgeon the most important clinical end point for the patient is graft patency. Dacron has become the material of choice in the high flow situation in wide bore vessels [1]. Knitted Dacron has superior handling characteristics compared to the more rigid and likely to fray woven Dacron, and it is better incorporated by the host tissues [2]. These two qualities of knitted Dacron are due to its high porosity which previously required a preclotting stage before insertion to render the graft impervious to blood. In the past a woven Dacron graft was preferred to a graft of knitted construction in resection of aortic aneurysm. This is because the size of the graft cannot be determined until the neck of the aneuFrom the Unitfor Peripheral Vascular Surgery, Glasgow Royal Infirmary, Glasgow, Scotland. Reprint requests: Mr. John G. Pollock, Unitfor Peripheral Vascular Surgery, Glasgow Royal Infirmary, Glasgow, Scotland.
rysm is dissected and intravenous heparin has been given [3]. Heparinization makes preclotting of the appropriate knitted graft impossible. A sealed graft overcomes this problem, allowing a graft of knitted construction to be used. A sealed graft that saves blood and hence transfusion is particularly important at a time when blood transfusion itself may be potentially harmful. These potential benefits of a sealed graft have been examined in this study together with the more important clinical end point of graft patency. Our clinical experience with more than 700 gelatinsealed implants is focused into a prospective study of the initial 100 patients undergoing aortic surgery in the Unit for Peripheral Vascular Surgery, Glasgow Royal Infirmary.
MATERIALS AND METHODS Gelseal aortic grafts* were implanted into 100 consecutive patients, 77 men, 23 women. The patients' mean age was 64 years (range 41-80). Their risk factors are shown in Table I. Fifty-one patients * Vascutek, Ltd., Inchinninan, Renfrewshire, Scotland.
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TABLE I.mNumber of patients with risk factors Cardiac history Hypertension Cerebral incident Family history of peripheral arterial disease Diabetes
31 18 10 9 5
were smokers immediately prior to surgery, another 46 patients were ex-smokers of greater than one month duration, and only three patients had never smoked before. Surgery was performed for aneurysm in 36 patients (including four with rupture), intermittent claudication in 44, rest pain in 17 and gangrene in three over a period of 18 months (August 1985 to February 1987). All surgery was carried out with prophylactic antibiotics using intravenous third generation cephalosporins at induction of anesthesia with two further doses over 24 hours. Systemic heparin (5,000 IU) was given prior to aortic crossclamping. This was reversed by protamine in a titrated dose. Intravenous volume loading was carried out by the anesthetist before declamping. The most common size of aortic graft was 16 x 8 mm (range 14 x 7 mm to 22 x 11 mm). Ninety-six aortic bifurcation grafts and four aortic tube grafts were inserted. The proximal anastomosis was end-to-side in 38 cases, end-to-end in 31, and the inlay technique for aneurysm performed in 31. Thirty-eight iliac and 153 femoral anastomoses were performed. There was one patient in whom only one distal anastomosis was performed because of the severity of arterial disease in the other limb with no adequate runoff. Operative lumbar sympathectomy was carried out concurrently in 36 patients, and five patients had extension grafts. There were two femoropopliteal bypass grafts, one bilateral femoropopliteal bypass, one tube extension from the lower limb of the aortic graft to the superficial femoral artery, and one extension graft from the lower limb of the graft to the profunda femoris artery. Four concurrent cholecystectomies were performed, and two cases also required reimplantation of the inferior mesenteric artery. Blood loss at surgery was monitored together with the need for blood transfusion and quantity transfused. The decision to transfuse blood was the anesthetist's. Blood transfusion was prescribed when blood loss at operation exceeded 750 ml and on clinical grounds in some patients when blood loss was less than 750 ml. An early complication was defined as occurring at less than 30 days from implantation and a late complication at more than 30 days. The patients were followed up prospectively and patency was assessed annually. The cohort was reviewed as a whole each year. Graft patency was
321
assessed clinically by palpation of pulses, and objectively by preoperative and postoperative ankle/ brachial pressure index (ABPI) and Doppler waveform analysis. All patients had postoperative ABPI and Doppler waveform analysis over the distal limbs of aortic bifurcation grafts. Four patients with aortic tube grafts were assessed without Doppler waveform analysis over the distal limbs of aortic bifurcation grafts. Four patients with aortic tube grafts were assessed without Doppler waveform analysis; all had normal peripheral pulses and normal ABPI. Where there was any doubt about patency, following clinical examination, ABPI, and Doppler waveform analysis, aortography was performed. This was only performed on four patients who had Doppler waveforms which were technically difficult to obtain. (This is in accordance with the standards and definitions described by the Ad Hoc Committee on Reporting Standards, Society for Vascular Surgery/North American Chapter, International Society for Cardiovascular Surgery [4]).
RESULTS Primary cumulative graft patency is 99% at 57 months follow-up. One limb of an aortic graft occluded at 15 months (Table II, Fig. 1). Perioperative mortality was 1%. One patient suffered a cerebrovascular accident 16 days after surgery and died. There was no measurable blood loss at implantation from the body of the sealed graft. The mean blood loss for each patient group is shown in Table III. The percentage of patients requiring blood transfusion for aneurysmal and occlusive disease is shown in Figure 2. Fifty-three patients did not require blood transfusion. Only 61% of patients with aneurysmal disease required blood transfusion and only 39% of patients with occlusive disease. During subsequent follow-up 12 deaths occurred. The causes of death are shown in Table IV. The commonest cause of death was myocardial infarction. All grafts were known to be patent immediately before death. Early complications
One patient developed lower limb ischemia immediately postoperatively. A popliteal embolectomy successfully retrieved atheromatous debris. Another patient occluded one limb of his graft immediately postoperatively, again embolic atheromatous "trash" material was successfully removed. One limb of a graft occluded eight days after implantation. At exploration a dissected intimal flap was repaired in the profunda femoris artery. These three cases were technical complica-
ANNALS OF VASCULAR SURGERY
PROSPECTIVE STUD Y OF GELATIN-SEALED GRAFTS
322
TABLE II.--Life table analysis No. withdrawn due to: Loss Death
Interval patency rate
Cumulative patency (%)
Standard error (%)
Interval (months)
No. at risk
No. failed
0-1
100
0
0
0
1.00
100
1-3
98
0
0
2
1.00
100
0
3-6 6-9 9-12
98 97 97
0 0 0
0 0 0
0 1 0
1.00 1.00 1.00
100 100 100
0 0 0
12-15
96
0
0
1
1.00
100
0
15-18 18-24 21-24 24-27 27-30 30-33 33-36 36-39 39-42 42-45 45-48 48-51 51-54 54-57
94 94 94 93 91 90 90 72 48 38 29 16 6 2
1 0 0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 0 0 0
1 0 0 0 2 1 0 2 2 0 0 0 0 0
0.99 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00
99 99 99 99 99 99 99 99 99 99 99 99 99 99
tions of the surgery and not related to the sealed graft. Another patient undergoing emergency revisional surgery for an occluded, nonsealed aortic graft inserted three years previously and who also had two thrombectomy procedures to a femoropopliteal extension graft one year previously, required a mid-thigh amputation. At insertion of the new sealed aortic graft the profunda femoris artery was too diseased to accept a limb of the graft. There were 10 patients with postoperative chest infection, two superficial groin wound infections, five patients who developed heart failure, one myocardial infarction and one pulmonary embolism. Two patients developed Legionnaires' disease immediately postoperatively (there was a point source outbreak of Legionnaires' disease in the hospital at this time involving 16 patients) [5]. Both of these two patients recovered; one patient developed a desquamation skin rash which was believed to be due to the antibiotics given for Legionnaires' disease.
0
1.02 1.02 1.02 1.02 1.02 1.04 1.04 1.04 1.06 1.06 1.06 1.06 1.06 1.06
anastomosed to the external iliac artery, and there was progression of arterial disease in the common femoral artery. This one occluded limb was successfully revised by a crossover graft from the patent limb of the aortic graft to the opposite profunda femoris artery with a short jump graft to the superficial femoral artery. Two patients developed ischemia due to progression of distal disease in the period of follow-up. One had recurrent ischemic rest pain two years after his aortic biprofunda graft. A femoropopliteal extension was performed, the sealed aortic graft was noted to be patent at operation. The femoropopliteal extension corrected a stenosis at the distal anastomosis. Both grafts continue to function and he no longer has rest pain. The other patient, who was diabetic, developed digital ischemic ulceration one year after an aortobifemoral graft. No further reconstructive surgery was possible as he had 100' 1 limb occluded at 15 months Number of
Late complications
One graft limb occluded at 15 months. At revisional surgery the occluded distal limb had been
aortic grafts at risk 50.
TABLE III.mMean blood loss for patient groups Mean Mean Total blood volume No. of no. Reason for loss (ml) patients of surgery (ml) transfused transfused patients Aneurysm Gangrene Rest pain Claudication
1170 850 792 771
770 650 450 440
22 2 7 16
36 3 17 44
0
0
12
24
36
48
Months
Fig. 1. Patency rate of aortic grafts with time.
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TABLE IV.--Cause of death
Month postoperative 2 9 14 17 26 27 28 31 36 38 40 41
Cause of death Ischemic heart disease Carcinoma of bladder Carcinoma of pancreas Carcinoma of liver Diverticular peritonitis Myocardial infarction Myocardial infarction Congestive cardiac failure Renal failure Chronic obstructive airways disease Cerebrovascular disease Myocardial infarction
m
Occlusive
Aneurysmal
Fig. 2. Percentage of patients requiring blood transfusion with aneurysm or occlusive disease,
patent superficial femoral and popliteal arteries. A digital amputation has been successful and this patient is currently well. One further patient complained of persistent groin discomfort, another has complained of impotence.
DISCUSSION This is a study of the first 100 patients who had gelatin-sealed aortic grafts implanted in Glasgow Royal Infirmary. The performance of this graft has been assessed in routine clinical practice with regard to the long-term patency and blood loss. This study is not randomized to compare unsealed grafts. Many such series of preclotted Dacron exist. By choosing 100 consecutive patients the authors believe that this was a realistic challenge to the graft when assessing patency and blood loss (the series includes 36 abdominal aortic aneurysms, four of which were ruptured and one inflammatory; 17 patients who had ischemic rest pain; and three with gangrene). The 99% cumulative patency rate at 57 months compares favorably with other series, however the authors do not claim that it is significantly
better than preclotted Dacron or polytetrafluoroethylene (PTFE) series since this present study was not randomized (Table V) [6-12]. Gelatin has been used safely for many years as a plasma expander [13]. The use of gelatin as a sealant allows the graft to be impervious to blood at implantation, and, being biodegradable, it may be removed within 14 days [14]. The rate of gelatin removal can be altered because of the nature of gelatin chemistry: reduction in cross-linkage is achieved by decreasing the number of available amino groups prior to exposure to formaldehyde. The reduction in cross-linkage speeds up its biodegradation, and the sealant also exhibits a relatively low thrombogenicity [15]. In vitro studies have assessed the safety of the gelatin-sealed graft treated by formaldehyde. They have shown the grafts to be nontoxic and nonmutagenic [2]. A major advantage of knitted grafts is their excellent healing properties, i.e., incorporation of the graft by the host. Granulation tissue in the form of fibroblasts and capillary buds penetrate the fabric within weeks, with knitted material being more porous than woven. This anchors the pseudointima and the prosthesis to the tissues. The gelatin-sealed graft is constructed with a low internal and high external velour. This enables the development of a thin, firm pseudointima and also rapid tissue ingrowth and incorporation [15]. This concept has been confirmed by another study: a
TABLE V.--Patency for aortic surgery Author Chang [6] Brewster [7] Petrovic [8] Karner [9] Cintora [10] Nevelsteen [11]
Year 1981 1978 1989 1988 1988 1980
Material Dacron Dacron PTFE PTFE/Dacron PTFE/Dacron Dacron
Vanttinen [12]
1975
Dacron
PTFE
-
Polytetrafluoroethylene
No. of patients 188 261 132 60/52 170/142 352 177
Years follow-up 6 5 4 2 4 5 10 5
Patency rate (%) 84 91 98.4 97/95 97/90 80 62 91
324
PROSPECTIVE STUD Y OF GELATIN-SEALED GRAFTS
high internal velour has been shown to produce a thick pseudointima [16]. The lack of inflammatory response to the sealant and its inherently low thrombogenicity may be important factors in long-term patency. In this context, we performed clinical studies measuring C-reactive protein and alpha-l-acid glycoprotein, and we have shown that gelatin-sealed grafts do not exaggerate the inflammatory response [17]. In vitro and clinical thrombogenicity studies assessed the gelatin-sealed Dacron compared to identical but untreated standard knitted Dacron. Gelatin-sealed grafts had significantly fewer platelets adhering when examined under the scanning electron microscope, suggesting that the gelatin-sealed graft has a lower thrombogenicity [18,19]. However the gelatin sealant is unlikely to contribute to long-term graft patency since it is rapidly removed by biodegradation. The 99% cumulative patency rate may reflect the graft skeleton and the consultancy-oriented practice of the unit.
CONCLUSIONS This prospective study showed a 99% cumulative patency rate at nearly five years follow-up (57 months). The sealed graft saves time and blood loss, important at a time when blood transfusion may be harmful. There was no problem related to the gelatin sealant. The gelatin-sealed graft has advantages over non-sealed Dacron. Its handling characteristics make it easy to use not only in the aortofemoral region, but we have obtained favorable results in above-knee femoropopliteal and axillofemoral regions where it can be tunnelled for distance, impervious to blood.
REFERENCES I, COOLEY DA. Development of vascular prosthesis to meet the surgeons requirements. In: GREENHALGH RM (ed). Diagnosis Techniques and Assessment Procedures in Vascular Surgery. London: Grune and Stratton, 1985, pp 493-502. 2. POLLOCK JG, DRURY JK, CUSCHIERI RJ, et al. New knitted Dacron prosthesis---experimental and clinical resuits. Rev Angiol Chir Vasc 1986;16:113-121.
mmm
ANNALS OF VASCULAR SURGERY
3. REID W, POLLOCK JG. A Surgeons Management of Gangrene. London: Pitman Medical, 1978. 4. RUTHERFORD RB, et al. Suggested standards for reports dealing with lower extremity ischemia. J Vasc Surg 1986;4: 80-94. 5. TIMBURY MC, DONALDSON JR, MC CARTNEY AC, et al. Outbreak of Legionnaires disease in Glasgow Royal Infirmary: microbiological aspects. J Hyg (Lond) 1986;97: 393-403. 6. CHANG JB. Surgical treatment of aorto-iliac artery disease. Angio 1981 ;32:73-105. 7. BREWSTER DC, DARLING RC. Optimal methods of aortoiliac reconstruction. Surgery 1978;84:739-748. 8. PETROVIC P, LOTINA S, DJORDJEVIC M, et al. Results of 132 PTFE (Gore-tex) bifurcated graft implantations. J Cardiovasc Surg 1989;30:897-901. 9. KARNER J, SCHEMPER M, TELEKY B, et al. Aorto-ybifurcation grafts: Dacron versus PTFE. Preliminary results of a randomized prospective study. Int Surg 1988;73:218220. I0. CINTORA I, PEARCE DE, CANNON JA. A clinical survey of aortobifemoral bypass using two inherently different graft types. Ann Surg 1988;208:625-630. 11. NEVELSTEEN A, SUY R, DAENEN A, et al. Aortofemoral grafting: factors influencing late results. Surgery 1980; 88:642-653. 12. VANTTINEN E, INBERG MV. Aorto-ilicofemoral arterial reconstructive surgery. Acta Chir Scand 1975;141:600-608. 13. LUNDSGAARD-HANSEN P, TSCHIRREN B. Clinical experience with 1200 units of modified fluid gelatin. Joint WHO/1985 Symposium on Standardization of Albumin and Plasma Substitutes, Geneva, 1986. Develop Biol Stand 4F Basel: S. Karger, 1981, pp 251-256. 14. GUIDOIN RJ, MARCEAU D, RAO TJ, et al. In vitro and in vivo characterization of an impervious polyester arterial prosthesis: the Gelseal triaxial graft. Biomaterials 1987;8: 433-441. 15. REID DB, POLLOCK JG. The gelatin pre-coated prosthesis. II Congresso Internazionalle Sulle Protesi Vascolari. Monduzzi Editore, 1989, pp 83-90. 16. WU H, ZAMMIT H, SAUVAGE LR, et al. The influence of inner wall filamentousness on the performance of small and large caliber arterial grafts. J Vasc Surg 1985;2:255-262. 17. VOHRA R, DRURY JK, SHAPIRO D, et al. Sealed versus unsealed Dacron prosthesis: a comparison of the acute phase protein response. Ann Vasc Surg 1987;1:548-551. 18. DRURY JK, ASHTON TR, CUNNINGHAM JD, et al. Experimental and clinical experience with a gelatin impregnated Dacron prosthesis. Ann Vasc Surg 1987;1:541-547. 19. ZAHRANI HA, CUSCHERI RJ, LOWE GDO, et al. Monoclonal antibody enzyme immunoassay in the study of thrombogenicity of preclotted and gelatin impregnated aortic prosthesis. Ann Vasc Surg 1989;4:248-250.
