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Role of urokinase in the superior mesenteric artery embolism
Brief clinical reports Role of urokinase in the superior mesenteric artery embolism Amando Moreno Gallego, MD, Pablo Ramirez, MD, Jose M. Rodriguez, MD, Francisco S. Bueno, MD, Ricardo Robles, MD, Antonio Capel, MD, and Pascual Parrilla, MD, Phi), Murcia, Spain
From the Department of Surgery, Hospital Virgen de la Arrixaca, University of Murcia, Murcia, Spain
SEVERAL STUDIES HAVE SHOWN r e c e n t l y t h a t i n t r a v e n o u s o r i n t r a a r t e r i a l u r o k i n a s e c a n p r o d u c e effective t h r o m bolysis i n d i f f e r e n t s i t u a t i o n s s u c h as a c u t e m y o c a r d i a l infarct, d e e p v e n o u s t h r o m b o s i s , a r t e r i a l t h r o m b o s i s o f the lower extremities, and pulmonary thromboembolism. 1 H o w e v e r , little clinical e x p e r i e n c e is available about the use of intraarterial urokinase infusion in mes e n t e r i c v a s c u l a r o c c l u s i o n . 2-4 T h i s article p r e s e n t s two cases o f s u p e r i o r m e s e n t e r i c a r t e r y (SMA) e m b o l i s m , b o t h o f w h i c h w e r e t r e a t e d successfully w i t h u r o k i n a s e i n f u s i o n . W e discuss t h e i n d i c a t i o n o f this t h e r a p e u t i c alternative.
CASE REPORTS Case 1. A 65-year-old m a n was admitted to the hospital with a history of arterial hypertension a n d repeated episodes of embolism, for which he received oral anticoagulants. Eight hours previously he h a d h a d a sudden onset of abdominal pain in the mesogastrium accompanied by diarrhea. Clinical examination revealed blood pressure of 130/70, irregular pulse, temperature of 36.8 ~ C, distended abdomen, which was tender but had no signs of abdominal rigidity, a n d bloodstained stools in the rectal exploration. Complementary examinations included normal chest and a b d o m e n X-ray films, electrocardiogram with atrial fibrillation, and analytics showing a white blood cell (WBC) count of 25,600 and p r o t h r o m h i n activity of 60%. Suspecting a mesenteric embolism we performed arteriography of the SMA, which showed an embolus beginning 2 to 3 cm from the ostium (Fig. 1, A). The catheter was positioned in contact with the embolus for urokinase infusion as follows: 500,000 IU in the first 2 hours, 250,000 IU in the following 2 hours, and 750,000 IU during a period of 12 hours. Four hours after the start of urokinase infusion the spontaneous abdominal pain disappeared, apart from a discrete pain Accepted for publication Oct. 11, 1995. Reprint requests: A. Moreno Ga|lego, Hospital u de la Aawixaca, Department of Surgery, Ctra. Murcia~Cartagena, 30120 El Palmar, Murcia, Spain. Surgery 1996;120:111-3. Copyright 9 1996 by Mosby-Year Book, Inc. 0039-6060/96/$5.00 + 0 11/57/71942
in response to deep palpation, without rigidity. The WBC count dropped to 16,000 and p r o t h r o m b i n activity to 43%. Fibrinogen levels were normal (550 m g / 1 0 0 ml). The arteriogram revealed an 85% dissolution of the embolus (Fig. 1, B). Twelve hours after the start of urokinase infusion the tenderness disappeared, the WBC c o u n t was normal, p r o t h r o m b i n activity remained stable at 45%, and the arteriogram showed complete dissolution of the embolus (Fig. 1, C). W h e n the urokinase infusion was finished, anticoagulation was begun with sodium heparin a n d parenteral feeding was instituted. The patient started to tolerate oral food intake and was discharged on day 18. Case 2. A 69-year-old woman was admitted to the hospital with a history of arterial hypertension and atrial fibrillation. She complained of a pain in the u p p e r a b d o m e n of some 6 hours' duration, together with nausea, vomiting, a n d diarrhea. The clinical examination revealed blood pressure of 160/80, temperature of 35.5 ~ C, regular pulse, abdominal tenderness in the mesogastrium without rigidity, and bloodstained stools in the rectal exploration. Complementary examinations included normal chest and a b d o m e n X-ray films, electrocardiogram without arrythmias, and analytics showing a WBC count of 10,400, hyperglucemia, and a p r o t h r o m b i n activity of 100%. Suspecting a inesenteric embolism we performed selective arteriography of the SMA, which revealed a distal embolic occlusion beyond the exit of the right colic artery (Fig. 2, A). We left the catheter in the vicinity of the embolus so that we could initiate intraarterial urokinase infusion by using the same regimen as with the previous case. Four hours after the start of urokinase infusion the spontaneous abdominal pain disappeared, apart from a slight pain in response to palpation, without rigidity. No fever was present. The analytics showed a WBC count of 23,600, p r o t h r o m b i n activity of 65.7%, and fibrinogen levels of 266 rag/100 ml. The arteriogram revealed dissolution of more than 80% of the erabolus (Fig. 2, B). Twelve hours after the start of urokinase infusion the abdominal tenderness disappeared completely, although stools still showed signs of blood. The analytics revealed a WBC count of 17,000 and p r o t h r o m b i n activity of 68%. The arteriogram showed complete repermeabilization of the artery (Fig. 2, 6). As with the previous case, when urokinase infusion was discontinued, heparin anticoagulation and parenteral feeding were instituted. O n the second day after urokinase treatment the patient experienced an episode of SURGERY
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Fig. 1. Case 1. A, Arteriogram of SMA shows embolus. B. Dissolution of 85% of embolus 4 hours after infusion of urokinase. C, Complete dissolution of embolus 12 hours later.
Fig. 2. Case 2. A, Complete obstruction of SMA. B, Dissolution of greater than 80% of embolus 4 hours later. C, Arteriogram 12 hours after infusion of urokinase shows complete dissolution of embolus.
cerebral embolism, confirmed by computed tomography, and persistence of bloodstained stools as a result of excess heparin, which led to suspension of the drug. After the neurologic symptoms improved, we instituted an oral diet and discharged the patient on day 45.
DISCUSSION I n n o r m a l medical practice, SMA embolism diagnosed by means of arteriography is an indication for emergency surgical embolectomy with a Fogarty tube a n d assessment of the n e e d to associate bowel resection. s-5 With the positive experience gained in fibrinolytic urokinase treatment for dissolving thrombi in various locations, 1 we opted for treating our two patients
initiallywith high-dose urokinase infusion for 4 hours by using the selective arteriography catheter ~-5 in the vicinity of the embolus. The fact that the two cases had a short history of symptoms (6 a n d 8 hours, respectively) a n d an absence of rigidity o n abdominal exploration was also a reason for us to indicate infusion as an alternative to surgical treatment. 4 T h e clinical response of our two patients to urokinase treatment was immediate; 4 hours after the start of infusion they were completely asymptomatic. The arteriogram showed almost complete dissolution of the erabolus in both cases (Figs. 1, B, a n d 2, B). Because the patients were asymptomatic after 4 hours, n o n e e d was present to perform a n exploratory laparotomy or laparoscopy to evaluate the presence of intestinal ischemic
Surgery Volume 120, Number 1
lesions. If surgery is implemented, a 5 mg bolus of r acid must be administered previously to eliminate the effects of circulating urokinase. 4 The systemic repercussions of urokinase o n coagulation, as also reported by others, were minimal; fibrinogen safety limits were always maintained. This seems to be connected with the fact that urokinase infusion was performed locally in situ a n d that the urokinase passes to the general circulation in smaller quantities. Both patients presented with a diarrhea syndrome for the first few days after urokinase infusion. This was interpreted as caused by the ischemic damage to the surface of the intestinal mucosa as a result of the episode of embolism, which n e e d e d this time to epithelialize a n d r e t u r n to normal. For this reason the patients were m a i n t a i n e d o n parenteral and then enteral feeding until they could tolerate the oral diet. We think that inclusion criteria for patients with this conservative therapy should be very strict: only in the event that the length of time from the onset of symptoms is shorter than 6 to 8 hours a n d peritoneal irritation is absent should patients be treated by intraarterial perfusion of urokinase. Furthermore, during perfusion, repermeabilization of the artery should be made evident, and, clinically, signs of peritoneal irritation
GaUego et al.
113
should n o t appear. I n the event that d u r i n g the first 4 hours such repermeabilization has n o t appeared or signs of peritoneal irritation appear, the patient will undergo a laparotomy to avoid the risk of intestinal necrosis. In conclusion, we present two cases of SMA embolism, diagnosed early, in which intraarterial urokinase infusion proves effective. This shows that in selected cases of mesenteric vascular occlusion, at least in centers where arteriographies can be performed, one should indicate thrombolysis with fibrinolytics, because surgical treatm e n t can be avoided a n d the patient cured. REFERENCES 1. PorterJM, GoodnightSH. The clinicaluse of fibrinolyticagenL~. AmJ Surg 1977;134:217-21. 2. RamlrezP, FelicesJM, SfichezBueno F, et al. Perfusi6nintra~rterial de urokinasaen la emboliade la arteria mesenttrica superior. Rev Esp Enferm Dig 1990;77:441-3. 3. Rodde A, PeiffertB, BazinC, Amrein D, Regent D, Mathieu P. Fibrinolyseintra-arterielled'une embolie de l'artere mesenterique supeieure.J Radiol 1991;72:239-42. 4. SchoembaumSW, Pena C, KoenigsbergP, Katzen BT. Superior mesenteric artery embolism:treatment with intraarterialurokinase.J Vasc Interv Radiol 1992;3:485-90. 5. ClavienPA.Diagnosisand managementofmesentericinfarction. BrJ Surg 1990;77:601-3.
B O U N D VOLUMES AVAILABLE T O SUBSCRIBERS
Bound volumes of Surgery are available to subscribers (only) for the 1996 issues from the publisher at a cost of $81.50 for domestic, $108.61 for Canadian, and $101.50 for in ternational subscribers for Vol. 119 (january to June) and Vol. 120 (July to December). Shipping charges are included. Each b o u n d volume contains a subject index and an author index, and all advertising is removed. Copies are shipped within 60 days after publication of the last issue in the volume. The binding is durable buckram with the JOURNALname, volume number, and year stamped in gold on the spine. Subscriptions must be in force to qualify. Bound volumes are not available in place of a regular journal subscription. Payment must accompany all orders. Contact Mosby-Year Book, Inc., Subscription Services, 11830 Westline Industrial Dr., St. Louis, MO 63146-3318; phone (800)325-4177, ext. 4351, or (314)453-4351.
From the Department of Surgery, Hospital Virgen de la Arrixaca, University of Murcia, Murcia, Spain
SEVERAL STUDIES HAVE SHOWN r e c e n t l y t h a t i n t r a v e n o u s o r i n t r a a r t e r i a l u r o k i n a s e c a n p r o d u c e effective t h r o m bolysis i n d i f f e r e n t s i t u a t i o n s s u c h as a c u t e m y o c a r d i a l infarct, d e e p v e n o u s t h r o m b o s i s , a r t e r i a l t h r o m b o s i s o f the lower extremities, and pulmonary thromboembolism. 1 H o w e v e r , little clinical e x p e r i e n c e is available about the use of intraarterial urokinase infusion in mes e n t e r i c v a s c u l a r o c c l u s i o n . 2-4 T h i s article p r e s e n t s two cases o f s u p e r i o r m e s e n t e r i c a r t e r y (SMA) e m b o l i s m , b o t h o f w h i c h w e r e t r e a t e d successfully w i t h u r o k i n a s e i n f u s i o n . W e discuss t h e i n d i c a t i o n o f this t h e r a p e u t i c alternative.
CASE REPORTS Case 1. A 65-year-old m a n was admitted to the hospital with a history of arterial hypertension a n d repeated episodes of embolism, for which he received oral anticoagulants. Eight hours previously he h a d h a d a sudden onset of abdominal pain in the mesogastrium accompanied by diarrhea. Clinical examination revealed blood pressure of 130/70, irregular pulse, temperature of 36.8 ~ C, distended abdomen, which was tender but had no signs of abdominal rigidity, a n d bloodstained stools in the rectal exploration. Complementary examinations included normal chest and a b d o m e n X-ray films, electrocardiogram with atrial fibrillation, and analytics showing a white blood cell (WBC) count of 25,600 and p r o t h r o m h i n activity of 60%. Suspecting a mesenteric embolism we performed arteriography of the SMA, which showed an embolus beginning 2 to 3 cm from the ostium (Fig. 1, A). The catheter was positioned in contact with the embolus for urokinase infusion as follows: 500,000 IU in the first 2 hours, 250,000 IU in the following 2 hours, and 750,000 IU during a period of 12 hours. Four hours after the start of urokinase infusion the spontaneous abdominal pain disappeared, apart from a discrete pain Accepted for publication Oct. 11, 1995. Reprint requests: A. Moreno Ga|lego, Hospital u de la Aawixaca, Department of Surgery, Ctra. Murcia~Cartagena, 30120 El Palmar, Murcia, Spain. Surgery 1996;120:111-3. Copyright 9 1996 by Mosby-Year Book, Inc. 0039-6060/96/$5.00 + 0 11/57/71942
in response to deep palpation, without rigidity. The WBC count dropped to 16,000 and p r o t h r o m b i n activity to 43%. Fibrinogen levels were normal (550 m g / 1 0 0 ml). The arteriogram revealed an 85% dissolution of the embolus (Fig. 1, B). Twelve hours after the start of urokinase infusion the tenderness disappeared, the WBC c o u n t was normal, p r o t h r o m b i n activity remained stable at 45%, and the arteriogram showed complete dissolution of the embolus (Fig. 1, C). W h e n the urokinase infusion was finished, anticoagulation was begun with sodium heparin a n d parenteral feeding was instituted. The patient started to tolerate oral food intake and was discharged on day 18. Case 2. A 69-year-old woman was admitted to the hospital with a history of arterial hypertension and atrial fibrillation. She complained of a pain in the u p p e r a b d o m e n of some 6 hours' duration, together with nausea, vomiting, a n d diarrhea. The clinical examination revealed blood pressure of 160/80, temperature of 35.5 ~ C, regular pulse, abdominal tenderness in the mesogastrium without rigidity, and bloodstained stools in the rectal exploration. Complementary examinations included normal chest and a b d o m e n X-ray films, electrocardiogram without arrythmias, and analytics showing a WBC count of 10,400, hyperglucemia, and a p r o t h r o m b i n activity of 100%. Suspecting a inesenteric embolism we performed selective arteriography of the SMA, which revealed a distal embolic occlusion beyond the exit of the right colic artery (Fig. 2, A). We left the catheter in the vicinity of the embolus so that we could initiate intraarterial urokinase infusion by using the same regimen as with the previous case. Four hours after the start of urokinase infusion the spontaneous abdominal pain disappeared, apart from a slight pain in response to palpation, without rigidity. No fever was present. The analytics showed a WBC count of 23,600, p r o t h r o m b i n activity of 65.7%, and fibrinogen levels of 266 rag/100 ml. The arteriogram revealed dissolution of more than 80% of the erabolus (Fig. 2, B). Twelve hours after the start of urokinase infusion the abdominal tenderness disappeared completely, although stools still showed signs of blood. The analytics revealed a WBC count of 17,000 and p r o t h r o m b i n activity of 68%. The arteriogram showed complete repermeabilization of the artery (Fig. 2, 6). As with the previous case, when urokinase infusion was discontinued, heparin anticoagulation and parenteral feeding were instituted. O n the second day after urokinase treatment the patient experienced an episode of SURGERY
111
112
Gallego et al.
Surgery July 1996
Fig. 1. Case 1. A, Arteriogram of SMA shows embolus. B. Dissolution of 85% of embolus 4 hours after infusion of urokinase. C, Complete dissolution of embolus 12 hours later.
Fig. 2. Case 2. A, Complete obstruction of SMA. B, Dissolution of greater than 80% of embolus 4 hours later. C, Arteriogram 12 hours after infusion of urokinase shows complete dissolution of embolus.
cerebral embolism, confirmed by computed tomography, and persistence of bloodstained stools as a result of excess heparin, which led to suspension of the drug. After the neurologic symptoms improved, we instituted an oral diet and discharged the patient on day 45.
DISCUSSION I n n o r m a l medical practice, SMA embolism diagnosed by means of arteriography is an indication for emergency surgical embolectomy with a Fogarty tube a n d assessment of the n e e d to associate bowel resection. s-5 With the positive experience gained in fibrinolytic urokinase treatment for dissolving thrombi in various locations, 1 we opted for treating our two patients
initiallywith high-dose urokinase infusion for 4 hours by using the selective arteriography catheter ~-5 in the vicinity of the embolus. The fact that the two cases had a short history of symptoms (6 a n d 8 hours, respectively) a n d an absence of rigidity o n abdominal exploration was also a reason for us to indicate infusion as an alternative to surgical treatment. 4 T h e clinical response of our two patients to urokinase treatment was immediate; 4 hours after the start of infusion they were completely asymptomatic. The arteriogram showed almost complete dissolution of the erabolus in both cases (Figs. 1, B, a n d 2, B). Because the patients were asymptomatic after 4 hours, n o n e e d was present to perform a n exploratory laparotomy or laparoscopy to evaluate the presence of intestinal ischemic
Surgery Volume 120, Number 1
lesions. If surgery is implemented, a 5 mg bolus of r acid must be administered previously to eliminate the effects of circulating urokinase. 4 The systemic repercussions of urokinase o n coagulation, as also reported by others, were minimal; fibrinogen safety limits were always maintained. This seems to be connected with the fact that urokinase infusion was performed locally in situ a n d that the urokinase passes to the general circulation in smaller quantities. Both patients presented with a diarrhea syndrome for the first few days after urokinase infusion. This was interpreted as caused by the ischemic damage to the surface of the intestinal mucosa as a result of the episode of embolism, which n e e d e d this time to epithelialize a n d r e t u r n to normal. For this reason the patients were m a i n t a i n e d o n parenteral and then enteral feeding until they could tolerate the oral diet. We think that inclusion criteria for patients with this conservative therapy should be very strict: only in the event that the length of time from the onset of symptoms is shorter than 6 to 8 hours a n d peritoneal irritation is absent should patients be treated by intraarterial perfusion of urokinase. Furthermore, during perfusion, repermeabilization of the artery should be made evident, and, clinically, signs of peritoneal irritation
GaUego et al.
113
should n o t appear. I n the event that d u r i n g the first 4 hours such repermeabilization has n o t appeared or signs of peritoneal irritation appear, the patient will undergo a laparotomy to avoid the risk of intestinal necrosis. In conclusion, we present two cases of SMA embolism, diagnosed early, in which intraarterial urokinase infusion proves effective. This shows that in selected cases of mesenteric vascular occlusion, at least in centers where arteriographies can be performed, one should indicate thrombolysis with fibrinolytics, because surgical treatm e n t can be avoided a n d the patient cured. REFERENCES 1. PorterJM, GoodnightSH. The clinicaluse of fibrinolyticagenL~. AmJ Surg 1977;134:217-21. 2. RamlrezP, FelicesJM, SfichezBueno F, et al. Perfusi6nintra~rterial de urokinasaen la emboliade la arteria mesenttrica superior. Rev Esp Enferm Dig 1990;77:441-3. 3. Rodde A, PeiffertB, BazinC, Amrein D, Regent D, Mathieu P. Fibrinolyseintra-arterielled'une embolie de l'artere mesenterique supeieure.J Radiol 1991;72:239-42. 4. SchoembaumSW, Pena C, KoenigsbergP, Katzen BT. Superior mesenteric artery embolism:treatment with intraarterialurokinase.J Vasc Interv Radiol 1992;3:485-90. 5. ClavienPA.Diagnosisand managementofmesentericinfarction. BrJ Surg 1990;77:601-3.
B O U N D VOLUMES AVAILABLE T O SUBSCRIBERS
Bound volumes of Surgery are available to subscribers (only) for the 1996 issues from the publisher at a cost of $81.50 for domestic, $108.61 for Canadian, and $101.50 for in ternational subscribers for Vol. 119 (january to June) and Vol. 120 (July to December). Shipping charges are included. Each b o u n d volume contains a subject index and an author index, and all advertising is removed. Copies are shipped within 60 days after publication of the last issue in the volume. The binding is durable buckram with the JOURNALname, volume number, and year stamped in gold on the spine. Subscriptions must be in force to qualify. Bound volumes are not available in place of a regular journal subscription. Payment must accompany all orders. Contact Mosby-Year Book, Inc., Subscription Services, 11830 Westline Industrial Dr., St. Louis, MO 63146-3318; phone (800)325-4177, ext. 4351, or (314)453-4351.