Intra-arterial thrombolytic therapy in the management of acute and chronic limb ischaemia

A group of 54 patients with acute or chronic limb ischaemia were initially treated with low dose intra-arterial thrombolytic therapy using streptokinase (10,000 units h-1) or plasminogen activator (0.5 mg h-1). Complete thrombolysis was obtained in 90 per cent of patients with symptoms of less than 1 week duration, and in 50 per cent with symptoms of greater than 1 week (P less than 0.05). Successful lysis in 36 patients was followed by successful bypass surgery in seven, percutaneous angioplasty in 13, no further treatment in 13, repeat thrombolysis in two and amputation in one. Failed therapy was associated with major amputation in 40 per cent. One patient died of haemorrhage and another of stroke as a direct result of thrombolytic treatment. The most common complication was haematoma at the site of cannulation of the vessel. Intra-arterial thrombolytic therapy can be very useful for the management of acute and chronic limb ischaemia, but complications do occur and patients should be carefully selected.     

Selective conservative and routine early operative treatment in acute limb ischaemia

Arterial thrombo-embolectomy is often unsuccessful in those patients with acute limb ischaemia that have peripheral arteriosclerosis. During this study, conservative heparin treatment and, when needed, delayed surgery was employed in acute limb ischaemia when the ischaemia was less severe as judged by assessment of distal motor and sensory functions, regardless of the presumed aetiology of the acute ischaemia. The results are compared with those during a preceding period, when the routine treatment was emergency thrombo-embolectomy. The emergency operation rate was reduced to 49 per cent. There were overall fewer deaths with gangrene (8 per cent versus 18 per cent). In acute arterial thrombosis, more good results were obtained (76 per cent versus 47 per cent), whereas results were unchanged in embolic cases despite the reduced emergency operation rate. This study suggests that the choice of initial treatment of patients with acute limb ischaemia may be based on the severity of the ischaemia, and that patients with less severe acute ischaemia benefit from initial conservative heparin treatment.     

A protocol for the safe treatment of acute lower limb ischaemia with intra-arterial streptokinase and surgery

Over a 5-year period 70 patients, presenting with subacute ischaemia of the lower limb (more than 12 h), were treated with low-dose intra-arterial streptokinase. There were 72 infusions and effective lysis was achieved in 52 (72 per cent), with an average infusion time of 25 h. A total of 23 (32 per cent) also underwent percutaneous transluminal angioplasty when lysis showed an underlying stenosis, and a further 19 (26 per cent) required surgery to remove persistent stenosis, organized thrombus or atheromatous debris. Significant bleeding occurred in 4 patients (6 per cent) and 13 (18 per cent) underwent amputation. There were five deaths (7 per cent), one of which was directly related to the infusion, while three were due to myocardial infarction. All of the major complications occurred in the early part of the study and both the selection of patients and the technique of infusion were modified to improve safety. Complementary treatment by percutaneous transluminal angioplasty and surgery was used more frequently in the later part of the study. The technique is not recommended for the white leg of acute ischaemia (less than 12 h), or for lysis of clot in a retroperitoneal Dacron graft, but may be uniquely valuable to demonstrate the cause of subacute ischaemia.     

Axillofemoral bypass as a limb salvage procedure in high risk patients with aortoiliac disease

Thirty-eight patients presenting with severe limb ischaemia and considered unfit for major aortic reconstruction underwent axillofemoral bypass as a limb salvage procedure. Four patients (11 per cent) died, including two who had presented with bilateral ischaemia secondary to acute aortic occlusion. The operative mortality rate for patients presenting with rest pain or ulceration/gangrene was 6 per cent. Cumulative 5-year survival and limb salvage were 44 per cent and 86 per cent respectively. Graft occlusion was the principal cause of worsening symptoms during follow-up (5-year primary patency of 68 per cent) and accounted for all major amputations of the operated limb. Axillounifemoral grafts had a significantly worse 5-year patency (50 per cent) than axillobifemoral grafts (80 per cent, P less than 0.05) and three of five patients who developed worsening symptoms in the non-operated limb died or required a major limb amputation as a consequence. Axillofemoral bypass is a valuable alternative to major aortic reconstruction in elderly patients and allows a greater proportion to be offered reconstruction than would otherwise be possible.     

Survey of the use of thrombolysis for acute limb ischaemia in the UK and Ireland

A total of 156 vascular surgeons from the UK and Ireland responded to a postal questionnaire on the use of thrombolysis in acute limb ischaemia. Almost half had used thrombolysis in the previous 12 months. Low dose intra-arterial streptokinase (89 per cent) was the regimen most frequently used, but 33 per cent had used intravenous streptokinase. Detailed results for 103 patients (limb salvage rate 60 per cent, amputation rate 35 per cent, mortality rate 5 per cent) were similar to those of previously published reports. Complications in most series were infrequent, but in the entire survey there were six bleeding-related deaths and one death from anaphylaxis. A total of 67 per cent of surgeons with working experience indicated that selected patients with acute arterial thromboses were most suitable for thrombolysis, particularly if there was no neurological deficit and no run-off for surgical bypass. Distal or late emboli and graft occlusions were regarded as appropriate by some surgeons. This study demonstrated that many vascular surgeons currently use thrombolysis, although sparingly and in selected cases. Patients with acute limb ischaemia should be managed by experienced vascular surgeons who are aware of the new therapeutic alternatives, an ideal supported by almost three-quarters of respondents to this survey.     

Morbidity and mortality in acute lower limb ischaemia: a 5-year review

A series of 204 consecutive patients with acute lower limb ischaemia was treated over a 5-year period in a Regional Vascular Unit. The mean age was 70 years, with a range of 41-98 and a female to male ratio of 1:0.94. Eighty-eight percent were treated by operation. Twenty-one had simultaneous vascular reconstructive procedures. Fifty-three patients died within 30 days (mortality rate 26%), and 12 required major amputation. Of these, four died resulting in a limb salvage rate of 95% in the survivors. An analysis of factors affecting outcome has shown increasing age, level of occlusion, recent myocardial infarction, pre-existing peripheral arterial disease and cardiopulmonary functional class to be major determinants of morbidity and mortality.     

Factors influencing the healing of distal amputations performed for lower limb ischaemia.

A total of 235 toes were amputated during 125 operations on 100 consecutive patients with lower limb ischaemia. The overall amputation wound healing rate for the series was 58.4 per cent and limb salvage was achieved in 66 patients. Toe amputation was performed under local anaesthesia in 57 cases and 32 (56 per cent) of these healed primarily, not significantly different from the healing rate of 41 (60 per cent) of 68 under general anaesthesia. Reconstructive arterial surgery was performed in conjunction with toe amputation in 39 patients; the healing rate with reconstruction was 32 (82 per cent) of 39, significantly better than the 41 (48 per cent) of 86 patients not undergoing bypass surgery (P less than 0.001). There was no difference in healing rates when comparing diabetic and non-diabetic patients. Multiple regression analysis demonstrated that reconstructive arterial surgery was the only factor which had an independent and significant influence on toe amputation healing. The use of local anaesthesia for distal amputation has no deleterious effects on wound healing.     

Results of a recently instituted programme of thrombolytic therapy in acute lower limb ischaemia

Twenty-eight patients with acute lower limb ischaemia received low dose intra-arterial thrombolytic therapy over a 2-year period. Eighteen patients received streptokinase and ten patients received recombinant tissue plasminogen activator (rTPA). Indications included arterial thromboemboli and graft failures. Mean ischaemic times were similar in both groups. Treatment time to achieve lysis was significantly less with rTPA (P less than 0.01). Subsequent vascular procedures, including angioplasty or reconstruction, were undertaken in 36 per cent of patients. Arterial puncture site bleeding occurred in eight (29 per cent) patients. Three (11 per cent) patients suffered rethrombosis after initial successful lysis. All rethromboses were successfully lysed with rTPA. There were two major amputations. Five (18 per cent) patients died, all lytic failures in the streptokinase treatment group. There were no cerebral haemorrhagic events and no patient died as a result of thrombolytic therapy. Good clinical outcome was obtained in nine of 18 patients treated with streptokinase and in nine of ten patients treated with rTPA. Intra-arterial thrombolysis provides effective therapy with high rates of limb salvage and a low mortality rate. This study suggests that rTPA may be a more effective agent, causing less morbidity, than streptokinase.     

Two-year follow-up after acute thromboembolic limb ischaemia: the importance of anticoagulation.

BACKGROUND: evidence on the effectiveness and usage of long-term anticoagulant therapy after acute thromboembolic limb ischaemia is very sparse. This study correlated medical events with administration of warfarin. METHOD: during a three-month audit in 1996, 287 patients with embolism or thrombosisin situ survived for 30 days, and 214 (75%) were reviewed by questionnaires returned from clinicians throughout the United Kingdom. Minimum follow-up was two years. RESULTS: thirty-five per cent had died. Recurrent acute limb ischaemia was reported in 11%, arterial intervention in 11%, and major amputation in 12%. Warfarin was given initially to 57% patients, but at follow-up only 43% were still taking warfarin (p<0. 05); reasons for stopping anticoagulation were often unknown. Recurrent limb ischaemia was less common in patients given warfarin initially (7% versus 17%) and still taking warfarin (3% versus 19%) -p;<0.05. Amputation was also less common in patients given warfarin initially (5% versus 21%) and still on warfarin (3% versus 21%) -p;<0.05. CONCLUSION: long-term oral anticoagulation was associated with reduced risk of recurrent limb ischaemia and amputation, but more research is needed to define the benefits and risks, especially for thrombosisin situ. Clinicians should give clear advice about anticoagulation when patients are discharged from hospital.     

Percutaneous transluminal angioplasty for lower limb ischaemia

Forty successful percutaneous transluminal angioplasties (PTA) were performed in the iliac and femoropopliteal segments of 33 patients with lower limb ischaemia. There was immediate symptomatic relief in 37 limbs (92 per cent) although 7 relapsed and 5 patients required reconstructive arterial surgery within a month of PTA. Objective testing showed that the longer term relapse rate (median follow-up 12 months) was low (10 per cent). Despite a significant incidence of early complications and relapse, PTA provided a good long term result in the majority of patients treated.     

Staged below-knee amputations for septic peripheral lesions due to ischaemia

Preservation of the knee joint is of paramount importance in lower limb amputation for ischaemia. Clinical predictors of healing are unreliable in patients with septic peripheral lesions due to ischaemia. Seventy-three patients in whom a below-knee amputation was considered likely to heal, based on the temperature and appearance of the skin and bleeding from skin and muscle flaps, were divided into two groups. Twenty-nine (Group A) had a primary below-knee (BK) amputation at the site of election with delayed primary skin closure, while 44 patients (Group B) initially had a guillotine BK amputation below the site of election, with elective amputation at the appropriate level once infection had been eradicated (4-5 days later). The groups were similarly matched with regard to level of occlusive arterial disease, nature of ischaemic lesions and operative risk factors. There was no significant difference in the overall operative mortality in Group A (6.7 per cent) compared with Group B (11.4 per cent) (P greater than 0.05). There was a significantly higher above-knee revision rate in Group A survivors (33.3 per cent) compared with Group B (7.7 per cent) (P less than 0.01) due to non-viability and uncontrolled sepsis of the BK amputation site. The presence or absence of a palpable femoral or popliteal pulse had no significant influence on healing in either group.     

Acute and chronic lower limb ischaemia

Limb ischaemia is a common clinical condition that causes considerable morbidity and mortality and represents a major drain on healthcare resources. Peripheral arterial disease (PAD) is the leading cause of both acute and chronic limb ischaemia. Chronic limb ischaemia may also be caused by non-atherosclerotic processes such as arterial entrapment, fibrosis or arteritis. Acute limb ischaemia may be also due to embolism, thrombosis or trauma. Duplex ultrasonography, computed tomography angiography and magnetic resonance angiography are now conventional forms of arterial imaging, with catheter angiography reserved for intervention. Risk factor modification is extremely important for all these patients, since many will also have significant coronary or cerebrovascular disease. Those with claudication often improve with structured exercise and if symptoms progress they may benefit from angioplasty or stenting. Arterial bypass remains the mainstay of treatment for patients with critical limb ischaemia if they are fit enough for surgery. Acute limb ischaemia is a surgical emergency and can be treated with surgical embolectomy or catheter-directed thrombolysis (depending on local expertise). Patients with irreversible limb ischaemia should be treated with primary amputation or palliation as appropriate.     

Early results of low dose intra-arterial streptokinase therapy in acute and subacute lower limb arterial ischaemia

Thirty-two patients with acute and subacute limb-threatening peripheral arterial ischaemia were treated with low dose intra-arterial streptokinase infusions. The mean duration of infusion was 38 h. Six patients developed pericatheter thrombosis and two had distal embolization of fragments of thrombus but in all cases these responded to repositioning the catheter and continuing the infusion. Five patients developed groin haematomata and in three of these there was evidence of a systemic fibrinolytic effect from the streptokinase with plasma fibrinogen reduced below 1 g/l. The most serious complication was perforation of the popliteal and tibial arteries which occurred on two occasions and required cessation of the infusion. Twenty-two patients (69 per cent) achieved limb salvage, eight (25 per cent) suffered a major amputation and two (6 per cent) died. The outcome was not related to the site, nature or duration of the arterial occlusion but patients with loss of sensation or paralysis of the affected limb were significantly less likely to obtain limb salvage (P = 0.001). For occlusions greater than 30 cm in length a new technique was used where the thrombus was lysed from distal to proximal in short lengths by gradual catheter withdrawal. This was successful in five out of six cases. Low dose intra-arterial streptokinase has been confirmed as an effective, relatively safe method of treatment in recent arterial ischaemia and can be recommended in situations where the results of surgery may not be favourable. In particular, patients with arterial thromboses and no distal run-off, distal and late arterial emboli, thrombosed popliteal aneurysms and patients after a failed embolectomy, have all been shown to respond to thrombolytic therapy with intra-arterial streptokinase.     

Increased limb salvage. Distal tibial/peroneal artery thrombectomy/embolectomy in acute lower extremity ischemia

Fifty-five acutely ischemic lower extremities, in 35 patients, which remained ischemic after standard thrombectomy/embolectomy techniques were further treated with distal tibial/peroneal thrombectomy/embolectomy by ankle level arteriotomy to increase limb salvage. A total of 84 infrapopliteal arteries were explored and thromboembolectomy performed in 79. The precipitating ischemic event was arterial embolus in 38 per cent, arterial thrombus in 60 per cent, and trauma in 2 per cent of the cases. There were 16 female and 19 male patients. Additional bypass grafting was used in 18 per cent of extremities. The limb salvage rate was 91 per cent in this select "tibial/peroneal" group. This technique salvaged 50 limbs that otherwise would have required major amputation. The addition of this technique changed the potential limb salvage rate from 76 per cent of the entire 199 lower extremities treated during this period to an actual limb salvage rate of 97 per cent. Operative mortality was 16 per cent in this selected group with an overall mortality of 6 per cent for all patients with acutely ischemic lower limbs. A mean patient follow-up of 32 months (range 12 to 72 months) identified only three late amputations, demonstrating that distal tibial/peroneal thrombectomy/embolectomy is a durable procedure. It is a technically easy means of promoting limb salvage in the acutely ischemic limb which either 1) remains ischemic after standard transinguinal iliofemoral thromboembolectomy, or 2) is secondary to infrapopliteal artery occlusion. It allows successful thromboembolectomy of acutely occluded infrapopliteal arteries without distal popliteal arteriotomy. These techniques should be within the armamentarium of all surgeons dealing with acute lower extremity ischemia.     

Do patients with critical limb ischaemia undergo multiple amputations after infrainguinal bypass surgery?

BACKGROUND: it has been suggested that an aggressive policy of bypass for limb salvage in critical ischaemia may result in patients subsequently undergoing multiple amputations. The aim of this study was to test this suggestion in the context of a dedicated Vascular Surgical Unit in a U.K. teaching hospital. METHODS: three hundred and sixty-eight patients undergoing lower limb bypass operations for critical limb ischaemia between April 1991 and March 1999 were studied retrospectively. Their median age was 69 years (IQR 64--75) and 243 (66%) were men. RESULTS: seventy-five operations were followed by one or more amputation (20%). Only 2% were multiple amputations. Age and sex had no effect on amputation rates, but emergency bypass operations led to a higher rate of amputation in those with critical limb ischaemia. CONCLUSION: patients with critical limb ischaemia who undergo lower limb bypass surgery rarely have subsequent multiple amputation.     

Major amputation compared with graft occlusion as the end point for assessing results of bypass surgery in lower limb ischaemia

Cumulative graft patency rates calculated using graft occlusion as the end point are the standard method of presenting results of bypass surgery for lower limb ischaemia. The problems of using graft occlusion as the end point are that this is not easily documented and it gives no indication of the condition of the patient's limb after the graft occludes. The date of amputation is a well defined end point and it means treatment has failed. It is used to calculate cumulative limb salvage rates. Using the two techniques to assess different risk factors (age, calf vessel run-off, diabetes, position of distal anastomosis and hypertension), it was found that the limb salvage rate was a better indicator of patient progress. Whereas graft patency rates for diabetics and non-diabetics were similar (chi 2 = 0.8, P greater than 0.1), diabetics had a higher amputation rate and the limb salvage rate was significantly worse (chi 2 = 5.0, P less than 0.05). Cumulative survival is rarely presented in vascular series but it could be used as an indicator of the general condition of patients being selected for bypass surgery. The cumulative survival of diabetics was 23 per cent (s.e.m. +/- 12 per cent) at four years, while for non-diabetics this was 55 per cent (s.e.m. +/- 15 per cent), (chi 2 = 10.6, P less than 0.001). Diabetic patients have such different limb salvage and survival rates compared with non-diabetic patients that their results should be presented separately. A better indication of patient progress following bypass surgery is obtained if limb salvage rates and survival rates are reported as well as graft patency rates.     

Preoperative assessment of the risk for cardiac death following thrombo-embolectomy for acute lower limb ischaemia.

Cardiac monitoring and the selective use of initial non-operative management is reported to reduce the high mortality rate in patients with acute lower limb ischaemia. Early estimation, prior to selection of initial therapy, of the risk for intraoperative or postoperative cardiac death following thrombo-embolectomy is therefore important. The aim of this prospective multi-centre study was to develop a simple and clinically useful index for assessment of the risk of post-operative cardiac death. Patients judged to need thrombo-embolectomy for acute lower limb ischaemia were evaluated on admission for routine clinical, cardiac and limb ischaemia parameters that could be related to cardiac function and these parameters compared to postoperative cardiac outcome. Sixteen per cent of the 117 patients died from intraoperative or postoperative cardiac complications. Analysis revealed five admission parameters that significantly and independently predicted a high risk for cardiac death: mean arterial blood pressure below 90 mmHg, clinical sign(s) of cardiac decompensation, ischaemia affecting the thigh, haemoglobin concentration exceeding 140 gl-1, and a history of a myocardial infarction in the previous 4 weeks. Definition of risk points for each risk factor allowed a simple classification of each patient into one of three significantly different cardiac risk classes with cardiac death rates of 6 +/- 3%, 27 +/- 8% and 75 +/- 16%, respectively. More than two thirds of the patients belonged to the low risk group. The described risk index provides a tool for preoperative assessment of the cardiac death risk associated with early thrombo-embolectomy in patients with acute lower limb ischaemia.     

Graft occlusion following aortofemoral bypass for peripheral ischaemia

Over a 10-year period, 241 patients with non-aneurysmal aortoiliac disease underwent aortofemoral bypass to 476 limbs. Four patients (1.7 per cent) occluded their grafts within 30 days of surgery, while 25 (10.4 per cent) suffered late graft occlusion. Postoperative occlusions were associated with significant morbidity and only one patient avoided major limb amputation or death. Overall, 46 episodes of graft thrombosis involving 51 graft limbs were encountered, the most common underlying cause being pre-existing or progressive multilevel distal occlusive disease. The overall cumulative graft patency rates were 95 and 87 per cent at 1 and 5 years respectively. Cumulative 5-year patency was significantly higher in patients presenting with claudication (91 per cent) than in patients presenting with rest pain (77 per cent) or ulceration and/or gangrene (71 per cent). Patients with evidence of multilevel distal occlusive disease at the time of aortic surgery had a significantly higher incidence of occlusion compared with those in whom there was no significant distal disease. In 35 episodes of occlusion (76 per cent), surgery was undertaken to restore limb blood flow, being successful in all but one case, with the most commonly performed procedure being graft limb thrombectomy. Seven of 28 patients (25 per cent) ultimately required major limb amputation and three patients died as a direct consequence of graft thrombosis.     

Acute embolic lower limb ischaemia is associated with decreased red cell deformability

Red cell deformability is an important determinant of peripheral blood flow. In this study the red cell filtration rate (RFR) was measured in 17 patients admitted for acute embolic lower limb ischaemia. The severity of the limb ischaemia on admission was scored from 0 to 6 depending on the degree of pain, and loss of motor and sensibility functions in the ischaemic extremity. Patients who presented with very severe ischaemia on admission underwent early embolectomy whereas those with less severe ischaemia (range from 0 to approximately 3 in ischaemic score) initially were treated conservatively with heparin. Red cell filtration rate was assessed with a standard microfiltration method and expressed in microliters/sec. On admission the RFR averages 30 +/- 5 microliters/sec (mean +/- S.D.), significantly lower than the corresponding value in a normal population of similar age (50 +/- 5 microliters/sec). There was an inverse relationship (r = 0.74, P less than 0.001 by use of linear regression analysis) between the ischaemic score and the RFR on admission, with low RFR values being related to high ischaemic scores. Forty-eight hours after revascularisation, the RFR had improved significantly in the patients having undergone successful revascularisation, whereas it was unchanged in conservatively treated patients. It is concluded that patients with acute embolic lower limb ischaemia have an impaired red cell filtration rate suggesting decreased red cell deformability, the impairment being related to the severity of the ischaemia. A poor red cell filtration rate on admission is related to increased risk of postoperative gangrene and/or cardiac death. Successful revascularisation, but not conservative heparin treatment is associated with increasing deformability.     

The influence of subintimal angioplasty on level of amputation and limb salvage rates in lower limb critical ischaemia: a 15-year experience.

OBJECTIVES: The aim of this study is to assess the influence of subintimal angioplasty (SIA) on lower limb amputation rate and level in critically ischaemic limbs. METHODS: Between January 1989 and March 2004, 1268 patients were admitted for treatment of lower limb critical ischaemia. Eight hundred and twenty-nine patients underwent revascularisation (bypass 671 and angioplasty 158), while 439 patients had primary amputations. A retrospective analysis of a prospectively maintained vascular registry was performed. Patients were divided into two groups, those who were admitted prior to the availability of subintimal angioplasty and those treated post-introduction of angioplasty. The two groups were compared with regards to age, sex, diabetes mellitus, ASA grade, Rutherford classification and level of disease. Outcome was assessed by the limb salvage rate, 30-day morbidity and mortality, and length of hospital stay. RESULTS: The average number of revascularisation increased with the introduction of subintimal angioplasty, from 53 to 96 per year (p<0.001). The overall limb salvage rate increased significantly from 42 to 70% (p<0.001). The cumulative limb salvage rate following revascularisation rose from 72 to 86% (p<0.001). The level of amputation (AKA:BKA) did not vary significantly. Thirty-day morbidity, mortality and length of hospital stay were significantly lower in the post-angioplasty group. CONCLUSIONS: Technical advances have resulted in a steadying of amputation numbers despite an ageing population.