The systemic fibrinolytic effect of BRL 26921 during the treatment of acute peripheral arterial occlusions.

BRL 26921 is a new acylated streptokinase-plasminogen complex which may have a more specific local thrombolytic effect than streptokinase or urokinase. 34 patients with acute peripheral arterial occlusions were given eight hourly bolus injections of 5 mg BRL 26921 for up to 72 h. Systemic fibrinolysis was observed in all patients yet in only 24% was the occluding thrombus lysed. 44% of the patients had haemorrhagic complications and 24% suffered further thrombotic events during or soon after treatment. There was no correlation between the degree of systemic fibrinolysis produced and dissolution of the thrombi. The degree of systemic fibrinolysis did not affect the complication rate. There is no evidence from this study that BRL 26921 has a specific local thrombolytic effect.

Fibrinolytic profiles in local low-dose thrombolysis with streptokinase and recombinant tissue plasminogen activator.

Fibrinolytic parameters have been monitored in 44 patients undergoing local low-dose intra-arterial thrombolysis for acute peripheral arterial ischaemia. Streptokinase (Sk), at a dose of 5,000 units/hr with 250 units/hr heparin, was used in 23 patients and recombinant tissue plasminogen activator (r-tPA) at a dose of 0.5 mg/hr was used in 21 patients. Successful lysis was seen in 18 (86%) patients following r-tPA and in 15 (65%) patients following streptokinase. There were 4 minor haematomas in each group usually at the catheter entry site. Both agents produced a systemic effect, which was still seen 12 hours post-infusion. However, that produced by r-tPA was delayed and significantly reduced compared to that produced by Sk. These results confirm the relative fibrin specificity of r-tPA. When used as a continuous low-dose intra-arterial infusion, r-tPA offers a significantly lower, potentially safer, systemic effect than conventional therapy with streptokinase.

A study of the use of the thromboxane A2 antagonist, sulotroban, in combination with streptokinase for local thrombolysis in patients with recent peripheral arterial occlusions: clinical effects, platelet function and fibrinolytic parameters.

In peripheral thrombolysis adjuvant anti-platelet therapy may help to lyse otherwise resistant thrombus, thereby increasing the number of patients successfully treated and reducing the "time to lysis". If continued after lysis it may help to prevent early rethrombosis. In this pilot study 21 patients undergoing peripheral thrombolysis with streptokinase were randomised to receive the thromboxane receptor antagonist sulotroban or placebo. The dose of sulotroban given was 2 mg/min (four patients), 4 mg/min (five patients) or 8 mg/min (four patients), eight patients received placebo. The clinical and laboratory effects of the treatment were monitored. Thrombolysis was achieved more quickly in patients receiving sulotroban, however, there was no difference between groups in the number of patients in whom recanalisation was achieved (six of eight receiving placebo and eight of 13 receiving sulotroban) or in the number of cases of early rethrombosis. During lysis there was an increase in plasma beta-thromboglobulin with similar levels being found in patients receiving sulotroban and streptokinase and those receiving streptokinase alone. No other major changes in platelet function during lysis were seen in patients receiving streptokinase alone. Sulotroban significantly reduced platelet aggregation and 14C-5HT release in response to several platelet agonists. With the thromboxane mimetic U46619 the degree of inhibition of aggregation and 14C-5HT release depended on the dose of sulotroban used. High levels of inhibition were associated with an excess of haemorrhagic complications especially in combination with a low plasma fibrinogen level. We conclude that the use of low dose sulotroban in combination with streptokinase merits further study and may hve a role in accelerating lysis.(ABSTRACT TRUNCATED AT 250 WORDS)

A bacteriological survey of amputation wound sepsis.

A retrospective survey of 100 lower limb amputations performed for ischaemia were analysed to assess the influence of preoperative bacterial isolates and the use of prophylactic antibiotics on wound sepsis. Forty-eight per cent had previously undergone a vascular procedure to attempt limb salvage and 17% were diabetics. Benzylpenicillin was given preoperatively and continued for 5 days; diabetics received metronidazole in addition. A total of 51 isolates were obtained from 30 patients preoperatively; Staphylococcus aureus and Enterobacteriaceae each accounted for over 25%. Postoperatively, 74 isolates (20 multiple) were obtained with an overall sepsis rate of 40%. Those patients with a positive preoperative culture were significantly more likely to develop wound sepsis. There was no significant difference in wound sepsis rates for diabetics. In view of the range of organisms causing postoperative infection, we recommend prophylaxis with a broad spectrum antibiotic for amputations.

Lower limb fractures with associated vascular injury.

We report the management and outcome of 35 lower limb fractures with associated severe vascular injuries treated over a 15-year period. Limb survival was related to the period of ischaemia. Management of the fractures by immediate open reduction and internal fixation was associated with a higher amputation rate than either external fixation or simple splintage, particularly for upper tibial injuries. External fixation is recommended as the method of choice for the stabilisation of the skeletal injury. A selective policy is advised for fasciotomy.

111In platelet deposition following peripheral arterial thrombolysis.

Streptokinase (Sk) and recombinant tissue plasminogen activator (rt-PA) have widely different effects on platelet aggregation. We have therefore undertaken a prospective evaluation of the deposition of indium-111 platelets following peripheral arterial thrombolysis. Seventeen patients were studied using autologous indium-111 labelled platelets. Patients were randomly allocated to receive 0.5 mg h-1 intra-arterial rt-PA (ten patients), or 5000 units h-1 Sk and 250 units h-1 heparin intra-arterially (seven patients). Initial uptake ratios (comparing affected limb to contra-lateral limb) at 24 h were usually low for both agents (medians: Sk 1.17; rt-PA 1.20) despite previous angioplasty or extensive thrombosis. There were minimally higher uptake ratios at 48 h and 72 h following Sk (1.64-1.45), than with intra-arterial rt-PA (0.93-1.43). Overall, two patients (one from each group) failed to achieve complete lysis or incurred early rethrombosis. Both were associated with a progressive increase in uptake ratio which was not present in those patients with successful initial lysis and continued patency at 30 days (1.18-0.94-1.19). We have been unable to demonstrate any significant difference in post-lysis platelet deposition between intra-arterial streptokinase and recombinant tissue plasminogen activator in this preliminary study. However, higher platelet deposition was associated with failure to achieve complete lysis and early rethrombosis. Concurrent therapy with antiplatelet agents may therefore be indicated in these patients.

A comparison between visual and quantitative analysis in a prospective evaluation of labelled 111In leucocyte imaging in vascular infection.

In a continuing evaluation of 111In-oxine labelled leucocyte imaging in vascular surgery, we have studied 16 patients with a clinical diagnosis of possible vascular graft infection. We have evaluated both visual and semi-quantitative analysis of the images obtained and have interpreted these in the light of the subsequent clinical outcome. Full length or multifocal uptake was seen in six patients, all of whom eventually required graft excision with two limbs surviving, and one death. These patients had a significantly higher uptake ratio (median = 3.26) than those with either localized (median = 1.12; p = 0.0027) or negative images (median = 0.72; p = 0.0003). Of four patients showing localized uptake only, one required amputation for continuing sepsis. Six patients had negative images, and had normal DSA and CT scans. Uptake ratios could not distinguish between those with localized images and those with negative images. Computer generated vertical profiles aided separation of patients with presumed localized and negative images. Semi-quantitative analysis has proved to be a reliable method which should allow a more direct comparison of the efficacy of various investigative techniques and of the results of therapy, independent of intra-observer subjective bias.

Some factors influencing hospital mortality in ruptured abdominal aortic aneurysms.

The factors which influenced hospital (or 30 day) mortality in 68 ruptured aortic aneurysms have been analysed. The most important factor determining the outcome is the depth of shock before the operation or related to this, the volume of blood transfused during or after operation or the duration of ventilatory support.

Resting plasma fibrinolytic activity and fibrinolytic potential in peripheral vascular disease.

Reduced plasma fibrinolytic activity may be a risk factor in venous and arterial thrombotic disease. Resting plasma fibrinolytic activity and fibrinolytic potential after ten minutes of venous occlusion were compared in 100 patients with peripheral vascular disease of varying severity and 20 age-sex matched controls. The fibrinolytic assay used was the euglobulin lysis time. Resting plasma fibrinolytic activity was significantly reduced in patients with a recent arterial thrombosis (p = 0.02) and ischaemic rest pain (p = 0.008) compared with controls. Fibrinolytic potential after venous occlusion was significantly reduced also in patients with a recent arterial thrombosis (p = 0.02) and ischaemic rest pain (p = 0.05) compared with controls. There were no significant differences between patients with claudication and controls. A reduced plasma fibrinolytic activity has been confirmed in patients with peripheral vascular disease and fibrinolytic potential may be a superior method of assessment as the euglobulin lysis time after venous occlusion is independent of the fibrinogen concentration. It remains uncertain whether the finding of reduced plasma fibrinolytic activity in patients with peripheral vascular disease is cause or effect and whether the finding has prognostic significance.

Tissue and serum concentrations of amoxycillin and clavulanic acid in patients having reconstructive vascular surgery.

Fifteen patients received amoxycillin/clavulanic acid combination intravenously at anaesthetic induction as part of a three-dose schedule of antibiotic prophylaxis for vascular surgery. After 30 min, the mean serum concentration of amoxycillin was 39.9 mg/l and clavulanic acid was 9.3 mg/l. Mean amoxycillin tissue concentrations in fat, 5.1 mg/l; vein, 7.5 mg/l; and artery, 4.8 mg/l, were lower than serum values. Mean clavulanic acid concentrations were: fat, 0.7 mg/l; vein, 1.2 mg/l; and artery, 1.6 mg/l. At the end of surgery, the serum amoxycillin level was always greater than 6 mg/l and clavulanic acid greater than 2 mg/l, which were both still within the therapeutic range. Concentrations in fat had declined by the end of the surgery ranging from 0.76 to 5.2 mg/l for amoxycillin and from 0.03 to 0.6 mg/l for clavulanic acid, there being almost none detected in four cases. Serum and tissue concentrations of both compounds 30 min after injection were sufficient to inhibit the growth of 97% of pathogenic organisms recovered from the skin of 135 vascular surgical patients. In a few cases tissue levels of the compounds were below inhibitory concentrations for coliforms and anaerobes at the time of skin closure, although they were still effective against most Gram-positive organisms. Amoxycillin/clavulanic acid combination is suitable antibiotic prophylaxis for vascular surgery.

Changing fashions in the surgery of aortic aneurysms.

A 10 year survey of patients undergoing surgery for abdominal aortic aneurysms is presented. If it is possible to use a straight graft, the postoperative 30 day mortality and morbidity is lower.

A review of 155 extra-anatomic bypass grafts.

Extra-anatomic bypass grafting has been used as treatment for patients with aorto-iliac disease who were considered unfit for aortic surgery. Eighty five percent of the patients had ischaemic pain at rest or skin necrosis. One hundred and three femorofemoral (FF) grafts, 40 axillounifemoral and 12 axillobifemoral grafts were performed. Femoropopliteal extension grafts were performed in 39 cases. The three year cumulative graft patency rate was 69% for FF grafts and 48% for both types of axillofemoral (AF) graft, falling to 61% for FF grafts and 32% for AF grafts at five years. The long term patient survival rate was poor, particularly for AF grafts, 27% at five years, reflecting the poor general condition of these patients. In addition almost a quarter of AF grafts required declotting at some stage. However, worthwhile limb salvage rates were obtained with both types of grafts, 69% for FF and 72% for AF at three years and 61% for FF and 65% for AF at five years, suggesting that these grafts should be employed as a means of avoiding amputation in poor risk patients.

A modified Gritti-Stokes amputation: its place in the management of peripheral vascular disease.

A modified technique for performing the Gritti-Stokes amputation is described and the results obtained in 247 cases are presented. The mortality rate was 9.3% and healing occurred in 87% of survivors. Using this modified technique the frequently cited criticisms of non-union of the patella and painful stumps were not found to be major problems. The prosthetic problems of amputation at this level are discussed in relation to recent developments in the design of artificial limbs.

Unoperated abdominal aortic aneurysm: presentation and natural history.

The natural history of abdominal aortic aneurysm (AAA) is death from rupture unless the patient dies from another cause prior to rupture. Elective aortic grafting is the treatment of choice. Following rupture, emergency operation is the only treatment which will prolong the patient's survival. Controversy still exists as to the optimum management in poor risk patients and in those with a small aneurysm. This paper describes the presentation and natural history of 65 patients presenting with a ruptured abdominal aortic aneurysm who did not have an emergency operation, and a further 27 patients in whom the diagnosis of intact AAA was made who did not have an elective aortic replacement graft. The correct diagnosis was made at the time of admission in only 43 of the 65 patients with ruptured aneurysms. The diagnostic errors and appropriate investigations in cases of doubt are discussed. The mean time from admission to hospital to death was 8 hours. The reasons for not performing an elective operation in the 27 patients known to have AAA are given. Nine have subsequently died from rupture. There have been 7 deaths from other causes.

Postoperative limb compression in reduction of haemorrhage after varicose vein surgery.

In varicose vein surgery, significant postoperative morbidity results from subcutaneous haematoma formation and limb swelling after saphenous vein stripping. We investigated the effectiveness of a high-compression short-stretch adhesive bandage compared with non-adhesive crêpe in reducing haemorrhage after stripping of varicose veins. Using 99mTc-labelled red blood cells, the degree of postoperative bleeding was assessed in 10 patients with bilateral varicose veins allocated for stripping and ligation. High-compression adhesive bandaging was applied to the experimental limb and a non-adhesive bandage to the contralateral control limb. Results show that adequate compression bandaging can decrease subcutaneous haematoma formation after stripping of varicose veins.

Role of Gritti-Stokes amputation in peripheral vascular disease.

The perigenicula lower limb amputations performed for peripheral vascular disease in Nottingham between April 1987 and September 1992 were reviewed. Of the 434 amputations, 173 were below-knee amputations (BKA), 144 Gritti-Stokes amputations (GSA) and 117 above-knee amputations (AKA). The 30-day mortality was significantly greater for AKA patients than either GSA or BKA patients. There was no difference in mortality within 30 days of amputation between GSA and BKA. Re-amputation rate to a more proximal level was significantly higher in BKA compared with GSA. Mobility after prosthetic rehabilitation was assessed using the Stanmore grading. A greater number of patients achieved mobility grade III and above in the GSA and BKA groups when compared with the AKA group, but there was no significant difference between GSA and BKA groups. At follow-up, a median of 23 months after amputation, there was a tendency for more patients to have given up using their limb prosthesis in the GSA group than either the BKA or AKA groups. However, there remained no significant difference between the BKA and GSA groups in the numbers of patients who remained successfully rehabilitated to Stanmore grade III or above. When a BKA is not possible, GSA offers a better prospect for rehabilitation compared with AKA in patients with occlusive arterial disease.

Five year experience using PTFE vascular grafts for lower limb ischaemia.

The 5 year results using polytetrafluoroethylene (PTFE-Gore-Tex) grafts mainly for superficial femoral occlusion have been reviewed. The majority of these grafts were inserted in an elderly poor risk group of patients with critical ischaemia of the lower limb. The overall cumulative patency at 2 years was 29% falling to 18% at 5 years. Further analyses were performed to take into account risk factors, namely, patient's age, diabetes, hypertension, continuation of smoking, peroperative angiographic findings and the site of the distal graft anastomosis. Peroperative angiographic run off was found to be the only risk factor significantly affecting the cumulative graft patency. The presence of diabetes was found to have a significant detrimental effect on limb salvage.

Popliteal artery aneurysm.

Fourteen patients with atherosclerotic aneurysms of the popliteal artery, which were bilateral in 13, have been managed in a vascular unit where ultrasound, xerography, and isotope angiography are available for investigation. Although these methods are useful in confirming a suspected diagnosis, they cannot replace an awareness of the condition and clinical methods of examining the ischaemic lower limb. Reconstructive vascular surgery was effective in preserving the presenting leg in 5 cases and amputation was needed in 6, while no operation was needed in 3. Elective arterial surgery was carried out on the asymptomatic contralateral leg in 7 cases with good results and this active approach to treatment is recommended.

Risk factors in vascular surgical sepsis.

The risk factors for sepsis after vascular surgery were studied in 100 consecutive patients with lower limb arterial ischaemia. Patients were randomised either to a short or long course of antibiotic prophylaxis with amoxycillin/clavulanic acid combination (Augmentin). Pathogenic organisms were isolated from the skin preoperatively in 39 (36%) cases, significantly more frequently in patients with ischaemic rest pain and skin necrosis (66%) than rest pain alone (21%) (P = 0.0004) or claudication/aneurysm (11%) (P = 0.0001). All but three organisms isolated (5%) were sensitive to amoxycillin/clavulanic acid. A wound infection occurred after 21 (19%) reconstructions, significantly more frequently both in patients suffering rest pain with skin necrosis (P = 0.001) and rest pain without skin necrosis (P = 0.04) compared with claudication/aneurysm. Sixteen of the 21 patients with a wound infection had at least one organism isolated from their skin preoperatively (P = 0.0001). Twelve patients (57%) had a similar organism isolated from the skin preoperatively and from the postoperative wound infection. Reducing the course of antibiotic prophylaxis from 5 days to 3 doses did not significantly increase the infection rate. The only other significant risk factor for sepsis was increasing age of the patient. Although prophylaxis is undisputed in patients having synthetic grafts, antibiotics may not be as important in the prevention of wound sepsis as had been thought. The role of antiseptic agents requires further evaluation.

A 10-year review of false aneurysms in Nottingham.

Over a 10-year period, twenty-nine patients who developed false aneurysms were reviewed retrospectively. The diagnosis was delayed for as long as 7 months in the eight patients who developed aneurysms following trauma. However, all these patients had an excellent outcome after surgery. The results were also good in patients with non-infected false aneurysms after vascular reconstruction, with 17 of the 19 patients having the affected limb saved by remedial surgery. The main principle of remedial surgery was to perform the simplest surgical procedure possible. The results in infected false aneurysms were poor and management should be considered along the lines laid down for graft infection. The incidence of false aneurysms may be reduced by the use of suitable non-absorbable sutures, prevention of tension at an anastomosis and prevention of infection. However, degeneration of the arterial wall is thought to be a major cause of false aneurysms and is, of course, beyond control. Recent technical advances such as digital subtraction angiography, labelled leucocyte scanning and computed tomography have all contributed to improvements in the management of false aneurysms.