- Email: [email protected]
Intra-Arterial Thrombolytic Therapy in the Initial Management of Thrombosed Popliteal Artery Aneurysms
Intra-Arterial Thrombolytic Therapy in the Initial Management of Thrombosed Popliteal Artery Aneurysms Ralph R. Garramone, Jr., MD, James J. Gallagher, Jr., MD, and A. David Drezner, MD, PhD, Hartford, Connecticut
Case reports of three patients presenting with acute limb-threatening lower extremity ischemia as a result of thrombosed popliteal artery aneurysms are described. Intra-arterial urokinase was administered to each patient prior to definitive surgery. This improved the infrapopliteal runoff in each case, allowing for successful arterial reconstruction without limb loss. (Ann Vasc Surg 1994;8:363-366.)
Aneurysms of the popliteal artery are the most commonly encountered peripheral aneurysms. Although rupture is rare, they are associated with a high incidence of thromboembolic complications and limb loss. In light of this unfavorable natural history, asymptomatic popliteal artery aneurysms are best managed by early diagnosis and appropriate elective surgical reconstruction. 1"2 Revascularization, performed urgently in the presence of acute limb ischemJa, is associated with an amputation rate of 20% to 38% and reduced graft patency compared with elective revascularization? "4 In addition, the number of patent infrapopliteal vessels has a direct impact on graft patency) '~ The administration of intra-arterial thrombolytic agents for acute arterial occlusive disease was introduced in the 1960s in an effort to concentrate the therapeutic effect and to decrease the hemorrhagic and systemic complications of From the Section of Vascular Surgery, Department of Surgery, University of Connecticut School of Medicine, Hartford Hospital, Hartford, Conn. Presented at The Third Annual Meeting of the Peripheral Vascular Surgery Society, Breckenridge, Colorado, January 2325, 1993. Reprint requests: A. David Drezner, MD, PhD, Chief, Section of Vascular Surgery, Department of Surgery, Hartford Hospital, Hartford, CT 06115.
intravenous infusion. It is n o w an effective therapeutic option in the management of selected patients with acute arterial occlusion. We report three cases of acute limb-threatening lower extremity ischemia secondary to popliteal artery aneurysm thrombosis initially treated with intra-arterial urokinase (Abbott Laboratories, North Chicago, Ill.). All three cases demonstrated initial obliteration of at least two of the infrapopliteal arteries. We believe that intra-arterial thrombolytic therapy restores patency of the infrapopliteal vessels and thus allows successful revascularization and limits limb loss. MATERIAL AND METHODS Each patient was evaluated initially by a history and physical examination followed by prompt arteriography. In the event that arteriography demonstrated a patent vessel or vessels distally suitable for bypass, the patient was scheduled for urgent surgical revascularization. If no such vessels were noted, the patient underwent either urgent surgical thrombectomy and intraoperative arteriography or intra-arterial urokinase administration in an effort to improve infrapopliteal runoff. Prior to the administration of intra-arterial urokinase, baseline coagulation parameters and a 363
Fig. 1. Initial arteriogranl demonstrating occlusion of the left popliteal artery by intraluminal thrombus.
Fig. 2. Initial arteriogram demonstrating runoff below the knee via collaterals only.
Fig. 3. Arteriogram following 24 hours of intra-arterial urokinase. The popliteal artery aneurysm is demonstrated and is now patent.
Fig. 4. Arteriogram after 24 hours of intra-arterial urokinase. The anterior tibial and peroneal arteries are now patent and open to the foot.
Vol. 8, No. 4 1994
Thrombolytic therapy in management of thrombosed popliteal artery aneurysms
Table I. P a t e n t infrapopliteal vessels before a n d a f t e r intra-arterial a d m i n i s t r a t i o n of u r o k i n a s e P a t e n t infrapopliteal vessels Case
Pre U K
P o s t UK
Total d o s e (units)
1
0
2
2,120~000
2 3
0 1
2 2
4,040,000 2,120,000
UK = urokinase.
c o m p l e t e blood c o u n t w e r e obtained. Following a r t e r i o g r a p h y the i n f u s i o n of u r o k i n a s e w a s beg u n at a rate of 240,000 units over the first hour, 120,000 units over the second hour, a n d 80,000 u n i t s / h r thereafter. I n e a c h case the i n f u s i o n w a s r u n c o n t i n u o u s l y via a c a t h e t e r w i t h m u l t i p l e side holes placed directly into the t h r o m b u s . The total d o s e of i n t r a - a r t e r i a l u r o k i n a s e a d m i n i s t e r e d to e a c h p a t i e n t is listed in Table I. C o n c o m i t a n t l o w - d o s e intra-arterial h e p a r i n w a s a d m i n i s t e r e d p r o x i m a l l y at a rate of 500 units/hr. E a c h of the p a t i e n t s w a s a d m i t t e d to the surgical s t e p - d o w n u n i t w h i l e the i n f u s i o n w a s in progress. T h e y w e r e m o n i t o r e d closely for develo p m e n t of a systemic lyric state. F i b r i n o g e n levels a n d platelet c o u n t s w e r e o b t a i n e d at regular intervals. No bleeding complications w e r e n o t e d in t h e s e patients, a n d n o blood t r a n s f u s i o n s w e r e required. F o l l o w - u p a r t e r i o g r a p h y w a s p e r f o r m e d 18 to 24 h o u r s a f t e r the initiation of t h e r a p y or as d e t e r m i n e d b y the clinical situation.
CASE R E P O R T S Case 1. A 56-year-old m a n presented 24 hours following the acute onset of left foot paresthesias that had progressed to severe claudication and rest pain. In the emergency department the patient was found to have an ischemic left lower extremity, and an emergency arteriogram demonstrated an occluded popliteal artery with intraluminal thrombus and runoff below the knee via collaterals only (Figs. 1 and 2). The patient was given intra-arterial urokinase via continuous infusion for 24 hours. A follow-up arteriogram demonstrated a 2 cm popliteal artery aneurysm partially filled with thrombus; the peroneal and anterior tibial arteries were now patent (Figs. 3 and 4). The urokinase was discontinued and the patient underwent an in situ femoral to below-knee popliteal artery bypass. The foot remained well perfused and had a palpable graft pulse. At 7-month follow-up he was free of ischemic symptoms. Case 2. A 68-year-old m a n with known atrial fibrillation presented with a cyanotic, cold, pulseless left foot. Femoral pulses were intact and equal bflater-
365
ally. A prominent popliteal pulse was palpable on the right but absent on the left. The initial arteriogram demonstrated complete occlusion of the superficial femoral artery with tittle runoff below the popliteal artery. The patient underwent operative thrombectomy, and an intraoperative artefiogram demonstrated a thrombosed popliteal artery aneurysm with no distal runoff. After 48 hours of intra-arterial urokinase via continuous infusion, the patient showed clinical signs of improvement. A follow-up arteriogram demonstrated a patent popliteal artery with runoff via a patent proximal anterior tibial artery that provided collateral flow to a distal peroneal artery patent to the foot. Then aneurysm exclusion and revascularization with an interposition Gore-Tex graft was performed. At 3-year follow-up the patient is free of ischemic symptoms on the left and has an ankle/brachial index of 0.96. He has not demonstrated symptoms of a popfiteal artery aneurysm on the right. Case 3. A 56-year-old. m a n presented with the sudden onset of left lower extremity pain and paresthesias and nocturnal rest pain. On physical examination the left foot was cold and pulseless. Examination of the right foot showed no abnormalities. The initial arteriogram demonstrated superficial femoral artery occlusion with reconstitution of the peroneal artery patent to the ankle and the anterior tihial artery patent only proximally. Clinical improvement was noted after continuous intra-arterial infusion of urokinase for 6 hours. A follow-up arteriogram at 24 hours demonstrated a widely patent superficial femoral artery, thrombus within a poptiteal artery aneurysm with a patent distal popliteal artery, and runoff via an anterior tibial artery and peroneal artery patent to the foot. The patient then underwent an in situ femoral to peroneal and posterior tibial artery bypass. The patient remains free of ischemic symptoms at 21 months follow-up and has an ankle/brachial index of 1.0. One m o n t h postoperatively he underwent arterial reconstruction because of embolic complications related to a popliteal aneurysm on the right.
DISCUSSION Popliteal artery a n e u r y s m t h r o m b o s i s is a wellrecognized c a u s e of acute limb ischemia. The n a t u r a l h i s t o r y of popliteal artery a n e u r y s m s t r e a t e d n o n s u r g i c a l l y is t h a t the m a j o r i t y will cause complications w R h i n 2 years of diagnosis. 2 I n m o s t cases s y m p t o m s result f r o m distal e m b o lization f r o m the a n e u r y s m . Less o f t e n local c o m pression m a y c a u s e neurologic findings or tenderness due to m a s s effect. C o n t i n u e d m i c r o e m b o lization leads to progressive occlusion of the infrapopliteal vessels, a n d a b n o r m a l arterial a n a t o m y b e l o w t h e popliteal artery c a n be d e m o n s t r a t e d in u p to 90% of these p a t i e n t s ? 's Obliteration of the r u n o f f vessels leads to gradually
366
Anfials of Vascular Surgery
Garramone et al.
reduced flow through the aneurysm, resulting in eventual thrombosis? The number of patent infrapopliteal vessels before and after intra-arterial administration of urokinase in each patient is listed in Table I. Graft patency has been shown to correlate with the presence of acute limb ischemia on presentation and with the anatomy of the infrapopliteal vessels. Shortell et al. 1 have reported 5-year graft patency rates of 92% following elective repair and 39% for patients treated in the presence of preoperative ischemic symptoms. In addition, patency rates increase with the number of patent infrapopliteal vessels. 1"~ Farina et al. ~ reported 4-year patency rates of 30% with no patent tibial vessels and 92% with one or more vessels open. Limb salvage, on the other hand, while unaffected by preoperative runoff, has been shown to be reduced in the presence of limb-threatening ischemia preoperatively. L4 The use of intra-arterial thrombolytic agents in patients with acute arterial occlusion has been well described. 6"7 In fact, as in the cases reported, intra-arterial thrombolytic therapy used in the setting of acute arterial occlusion has led to the diagnosis of popliteal artery aneurysm after thrombolysis. 8 The relative and absolute contraindications to both systemic and intra-arterial lyric therapy have been outlined by Quin6nes-Baldrich? Although the presence of an associated aneurysm in the patient with a popliteal artery aneurysm is well recognized, it is not a contraindication to either systemic or intra-arterial thrombolysis. CONCLUSION In the cases reported the early use of intra-arterial urokinase proved to be an effective method of
identifying the underlying lesion, optimizing tibial vessel runoff, and restoring limb perfusion in the acutely ischemic lower extremity secondary to popliteal artery aneurysm thrombosis. The last two effects, optimizing tibial vessel runoff and restoring limb perfusion, have both been shown to have a favorable impact on graft patency and amputation rate. Lyric therapy in the presence of popliteal artery aneurysm thrombosis should improve long-term patency and limit limb loss.
REFERENCE S 1. Shorten CK, DeWeese JA, Ouriel K, et al. Popliteal artery aneurysms: A 25-year surgical experience. J Vasc Surg 1991; 14:771-779. 2. Dawson IM, van Bockel H, Brand R, et al. Popliteal artery aneurysm: Long-term follow up of aneurysmal disease and results of surgical treatment. J Vasc Surg 1991;13:398-407. 3. Lilly ME Flyrm WR, McCarthy WJ III, et al. The effect of distal arterial anatomy on the success of popliteal aneurysm repair. J Vasc Surg 1988;7:653-660. 4. Anton GE, Hertzer NR, Beven EG, et al. Surgical management of popliteal aneurysms. Trends in presentation, treatment, and results from 1952 to 1984. J Vasc Surg 1986;3:125-134. 5. Farina C, Cavallaro A, Schultz RD, et al. Popliteal aneurysms. Surg Gynecol Obstet 1989;169:7-13. 6. Belkin M, Belkin B, Bucknam CA, et al. Intra-arterial fibrinolytic therapy. Efficacy of streptokinase vs. urokinase. Arch Surg 1986;121:769-773. 7. Comerata AJ, Rubin RN, Tyson RR, et al. Intra-arterial thrombolytic therapy in peripheral vascular disease. Surg Gynecol Obstet 1987;165:1-8. 8. Lancashire MJR, Torrie EPH, Galland RB. Popliteal aneurysms identified by intra-arterial streptokinase: A changing pattern of presentation. Br J Surg 1990;77:1388-1390. 9. Quin6nes-Baldrich WJ. Thrombolytic therapy for vascular disease. In Moore WS, ed. Vascular Surgery: A Comprehensive Review. Philadelphia: WB Saunders, 1993, pp 313-339.
Case reports of three patients presenting with acute limb-threatening lower extremity ischemia as a result of thrombosed popliteal artery aneurysms are described. Intra-arterial urokinase was administered to each patient prior to definitive surgery. This improved the infrapopliteal runoff in each case, allowing for successful arterial reconstruction without limb loss. (Ann Vasc Surg 1994;8:363-366.)
Aneurysms of the popliteal artery are the most commonly encountered peripheral aneurysms. Although rupture is rare, they are associated with a high incidence of thromboembolic complications and limb loss. In light of this unfavorable natural history, asymptomatic popliteal artery aneurysms are best managed by early diagnosis and appropriate elective surgical reconstruction. 1"2 Revascularization, performed urgently in the presence of acute limb ischemJa, is associated with an amputation rate of 20% to 38% and reduced graft patency compared with elective revascularization? "4 In addition, the number of patent infrapopliteal vessels has a direct impact on graft patency) '~ The administration of intra-arterial thrombolytic agents for acute arterial occlusive disease was introduced in the 1960s in an effort to concentrate the therapeutic effect and to decrease the hemorrhagic and systemic complications of From the Section of Vascular Surgery, Department of Surgery, University of Connecticut School of Medicine, Hartford Hospital, Hartford, Conn. Presented at The Third Annual Meeting of the Peripheral Vascular Surgery Society, Breckenridge, Colorado, January 2325, 1993. Reprint requests: A. David Drezner, MD, PhD, Chief, Section of Vascular Surgery, Department of Surgery, Hartford Hospital, Hartford, CT 06115.
intravenous infusion. It is n o w an effective therapeutic option in the management of selected patients with acute arterial occlusion. We report three cases of acute limb-threatening lower extremity ischemia secondary to popliteal artery aneurysm thrombosis initially treated with intra-arterial urokinase (Abbott Laboratories, North Chicago, Ill.). All three cases demonstrated initial obliteration of at least two of the infrapopliteal arteries. We believe that intra-arterial thrombolytic therapy restores patency of the infrapopliteal vessels and thus allows successful revascularization and limits limb loss. MATERIAL AND METHODS Each patient was evaluated initially by a history and physical examination followed by prompt arteriography. In the event that arteriography demonstrated a patent vessel or vessels distally suitable for bypass, the patient was scheduled for urgent surgical revascularization. If no such vessels were noted, the patient underwent either urgent surgical thrombectomy and intraoperative arteriography or intra-arterial urokinase administration in an effort to improve infrapopliteal runoff. Prior to the administration of intra-arterial urokinase, baseline coagulation parameters and a 363
Fig. 1. Initial arteriogranl demonstrating occlusion of the left popliteal artery by intraluminal thrombus.
Fig. 2. Initial arteriogram demonstrating runoff below the knee via collaterals only.
Fig. 3. Arteriogram following 24 hours of intra-arterial urokinase. The popliteal artery aneurysm is demonstrated and is now patent.
Fig. 4. Arteriogram after 24 hours of intra-arterial urokinase. The anterior tibial and peroneal arteries are now patent and open to the foot.
Vol. 8, No. 4 1994
Thrombolytic therapy in management of thrombosed popliteal artery aneurysms
Table I. P a t e n t infrapopliteal vessels before a n d a f t e r intra-arterial a d m i n i s t r a t i o n of u r o k i n a s e P a t e n t infrapopliteal vessels Case
Pre U K
P o s t UK
Total d o s e (units)
1
0
2
2,120~000
2 3
0 1
2 2
4,040,000 2,120,000
UK = urokinase.
c o m p l e t e blood c o u n t w e r e obtained. Following a r t e r i o g r a p h y the i n f u s i o n of u r o k i n a s e w a s beg u n at a rate of 240,000 units over the first hour, 120,000 units over the second hour, a n d 80,000 u n i t s / h r thereafter. I n e a c h case the i n f u s i o n w a s r u n c o n t i n u o u s l y via a c a t h e t e r w i t h m u l t i p l e side holes placed directly into the t h r o m b u s . The total d o s e of i n t r a - a r t e r i a l u r o k i n a s e a d m i n i s t e r e d to e a c h p a t i e n t is listed in Table I. C o n c o m i t a n t l o w - d o s e intra-arterial h e p a r i n w a s a d m i n i s t e r e d p r o x i m a l l y at a rate of 500 units/hr. E a c h of the p a t i e n t s w a s a d m i t t e d to the surgical s t e p - d o w n u n i t w h i l e the i n f u s i o n w a s in progress. T h e y w e r e m o n i t o r e d closely for develo p m e n t of a systemic lyric state. F i b r i n o g e n levels a n d platelet c o u n t s w e r e o b t a i n e d at regular intervals. No bleeding complications w e r e n o t e d in t h e s e patients, a n d n o blood t r a n s f u s i o n s w e r e required. F o l l o w - u p a r t e r i o g r a p h y w a s p e r f o r m e d 18 to 24 h o u r s a f t e r the initiation of t h e r a p y or as d e t e r m i n e d b y the clinical situation.
CASE R E P O R T S Case 1. A 56-year-old m a n presented 24 hours following the acute onset of left foot paresthesias that had progressed to severe claudication and rest pain. In the emergency department the patient was found to have an ischemic left lower extremity, and an emergency arteriogram demonstrated an occluded popliteal artery with intraluminal thrombus and runoff below the knee via collaterals only (Figs. 1 and 2). The patient was given intra-arterial urokinase via continuous infusion for 24 hours. A follow-up arteriogram demonstrated a 2 cm popliteal artery aneurysm partially filled with thrombus; the peroneal and anterior tibial arteries were now patent (Figs. 3 and 4). The urokinase was discontinued and the patient underwent an in situ femoral to below-knee popliteal artery bypass. The foot remained well perfused and had a palpable graft pulse. At 7-month follow-up he was free of ischemic symptoms. Case 2. A 68-year-old m a n with known atrial fibrillation presented with a cyanotic, cold, pulseless left foot. Femoral pulses were intact and equal bflater-
365
ally. A prominent popliteal pulse was palpable on the right but absent on the left. The initial arteriogram demonstrated complete occlusion of the superficial femoral artery with tittle runoff below the popliteal artery. The patient underwent operative thrombectomy, and an intraoperative artefiogram demonstrated a thrombosed popliteal artery aneurysm with no distal runoff. After 48 hours of intra-arterial urokinase via continuous infusion, the patient showed clinical signs of improvement. A follow-up arteriogram demonstrated a patent popliteal artery with runoff via a patent proximal anterior tibial artery that provided collateral flow to a distal peroneal artery patent to the foot. Then aneurysm exclusion and revascularization with an interposition Gore-Tex graft was performed. At 3-year follow-up the patient is free of ischemic symptoms on the left and has an ankle/brachial index of 0.96. He has not demonstrated symptoms of a popfiteal artery aneurysm on the right. Case 3. A 56-year-old. m a n presented with the sudden onset of left lower extremity pain and paresthesias and nocturnal rest pain. On physical examination the left foot was cold and pulseless. Examination of the right foot showed no abnormalities. The initial arteriogram demonstrated superficial femoral artery occlusion with reconstitution of the peroneal artery patent to the ankle and the anterior tihial artery patent only proximally. Clinical improvement was noted after continuous intra-arterial infusion of urokinase for 6 hours. A follow-up arteriogram at 24 hours demonstrated a widely patent superficial femoral artery, thrombus within a poptiteal artery aneurysm with a patent distal popliteal artery, and runoff via an anterior tibial artery and peroneal artery patent to the foot. The patient then underwent an in situ femoral to peroneal and posterior tibial artery bypass. The patient remains free of ischemic symptoms at 21 months follow-up and has an ankle/brachial index of 1.0. One m o n t h postoperatively he underwent arterial reconstruction because of embolic complications related to a popliteal aneurysm on the right.
DISCUSSION Popliteal artery a n e u r y s m t h r o m b o s i s is a wellrecognized c a u s e of acute limb ischemia. The n a t u r a l h i s t o r y of popliteal artery a n e u r y s m s t r e a t e d n o n s u r g i c a l l y is t h a t the m a j o r i t y will cause complications w R h i n 2 years of diagnosis. 2 I n m o s t cases s y m p t o m s result f r o m distal e m b o lization f r o m the a n e u r y s m . Less o f t e n local c o m pression m a y c a u s e neurologic findings or tenderness due to m a s s effect. C o n t i n u e d m i c r o e m b o lization leads to progressive occlusion of the infrapopliteal vessels, a n d a b n o r m a l arterial a n a t o m y b e l o w t h e popliteal artery c a n be d e m o n s t r a t e d in u p to 90% of these p a t i e n t s ? 's Obliteration of the r u n o f f vessels leads to gradually
366
Anfials of Vascular Surgery
Garramone et al.
reduced flow through the aneurysm, resulting in eventual thrombosis? The number of patent infrapopliteal vessels before and after intra-arterial administration of urokinase in each patient is listed in Table I. Graft patency has been shown to correlate with the presence of acute limb ischemia on presentation and with the anatomy of the infrapopliteal vessels. Shortell et al. 1 have reported 5-year graft patency rates of 92% following elective repair and 39% for patients treated in the presence of preoperative ischemic symptoms. In addition, patency rates increase with the number of patent infrapopliteal vessels. 1"~ Farina et al. ~ reported 4-year patency rates of 30% with no patent tibial vessels and 92% with one or more vessels open. Limb salvage, on the other hand, while unaffected by preoperative runoff, has been shown to be reduced in the presence of limb-threatening ischemia preoperatively. L4 The use of intra-arterial thrombolytic agents in patients with acute arterial occlusion has been well described. 6"7 In fact, as in the cases reported, intra-arterial thrombolytic therapy used in the setting of acute arterial occlusion has led to the diagnosis of popliteal artery aneurysm after thrombolysis. 8 The relative and absolute contraindications to both systemic and intra-arterial lyric therapy have been outlined by Quin6nes-Baldrich? Although the presence of an associated aneurysm in the patient with a popliteal artery aneurysm is well recognized, it is not a contraindication to either systemic or intra-arterial thrombolysis. CONCLUSION In the cases reported the early use of intra-arterial urokinase proved to be an effective method of
identifying the underlying lesion, optimizing tibial vessel runoff, and restoring limb perfusion in the acutely ischemic lower extremity secondary to popliteal artery aneurysm thrombosis. The last two effects, optimizing tibial vessel runoff and restoring limb perfusion, have both been shown to have a favorable impact on graft patency and amputation rate. Lyric therapy in the presence of popliteal artery aneurysm thrombosis should improve long-term patency and limit limb loss.
REFERENCE S 1. Shorten CK, DeWeese JA, Ouriel K, et al. Popliteal artery aneurysms: A 25-year surgical experience. J Vasc Surg 1991; 14:771-779. 2. Dawson IM, van Bockel H, Brand R, et al. Popliteal artery aneurysm: Long-term follow up of aneurysmal disease and results of surgical treatment. J Vasc Surg 1991;13:398-407. 3. Lilly ME Flyrm WR, McCarthy WJ III, et al. The effect of distal arterial anatomy on the success of popliteal aneurysm repair. J Vasc Surg 1988;7:653-660. 4. Anton GE, Hertzer NR, Beven EG, et al. Surgical management of popliteal aneurysms. Trends in presentation, treatment, and results from 1952 to 1984. J Vasc Surg 1986;3:125-134. 5. Farina C, Cavallaro A, Schultz RD, et al. Popliteal aneurysms. Surg Gynecol Obstet 1989;169:7-13. 6. Belkin M, Belkin B, Bucknam CA, et al. Intra-arterial fibrinolytic therapy. Efficacy of streptokinase vs. urokinase. Arch Surg 1986;121:769-773. 7. Comerata AJ, Rubin RN, Tyson RR, et al. Intra-arterial thrombolytic therapy in peripheral vascular disease. Surg Gynecol Obstet 1987;165:1-8. 8. Lancashire MJR, Torrie EPH, Galland RB. Popliteal aneurysms identified by intra-arterial streptokinase: A changing pattern of presentation. Br J Surg 1990;77:1388-1390. 9. Quin6nes-Baldrich WJ. Thrombolytic therapy for vascular disease. In Moore WS, ed. Vascular Surgery: A Comprehensive Review. Philadelphia: WB Saunders, 1993, pp 313-339.