I
Case Report
Fibrinolytic Therapy in a Patient with Denver Peritoneovenous Shunt Occlusion1 Neil J. Halin, DO Lewis M. Halin, DO
Index terms: Ascites, 791.77 Shunts, peritoneovenous, 95,4539,982,4539 Thrombolysis Urokinase
Urokinase thrombolytic therapy was used on three separate occasions to lyse thrombosed Denver peritoneovenous shunts in a 51-year-old woman. Shunt patency was preserved over a 2-yearperiod, with a fatal complicationfollowing the third procedure. The authors suggest that thrombolytic therapy might be a viable alternative to immediate surgical revision in patients with failed Denver shunts.
JVIR 1992; 3:135-139 Abbreviations: DIC = disseminated intravascular coagulopathy, FSP = fibrin split product, MAA = macroaggregates of albumin, PT = prothrombin time, PTT = partial thromboplastin time
' From the Department of Radiology, Metropolitan Hospital-Central Division, Philadelphia. Received May 17, 1991; revision requested June 20; revision received August 12; accepted August 22. Address reprint requests to N.J.H., 155 Dale St, Dedham, MA 02026. SCVIR, 1992
T H E use of peritoneovenous shunting of ascites with a manmade device was pioneered by Smith in 1962. Using a modified Spitz-Holter hydrocephalus drain, he proved peritoneocaval shunting was possible (1). The LeVeen shunt, a rigid plastic chamber housing a pressure-sensitive, one-way valve, was introduced in 1974 as the first job-specific peritoneovenous shunt. The Denvertype peritoneovenous shunt was introduced in 1979 and features a flexible pumping chamber and single-miter valve (2) (Fig 1).The valve opens at a positive pressure of 1cm of water and closes rapidly to prevent retrograde flow. Crystalline heparin is bonded to the lumen of the tubing and valve to help prevent thrombus formation. Since their introduction, the LeVeen and Denver shunts have been applied to the management of ascites due to various causes (3-8). Shunt failure and failure of surgically revised shunts due to occlusion are known to occur. Shunt occlusion in nonmalignant ascites may be due to fibrin aggregates or frank luminal thrombus formation. Both of these should be amenable to fibrinolysis or thrombolysis. Here, we present results of three episodes of nonsurgical shunt salvage in a single patient with use of the fibrinolytic drug urokinase (Abbokinase; Abbott Laboratories, North Chicago, Ill).
CASE REPORT Three occurrences of Denver shunt occlusion were treated in a 51-year-old
woman over a 2-year period. A singlevalve Denver peritoneovenous shunt (Denver Biomaterials, Evergreen, Colo) was placed in the patient for relief of ascites secondary to cirrhosis and chronic renal failure requiring hemodialysis. Following successful fibrinolysis, the first shunt became dislodged from the central venous system and a second shunt was placed. After each of two episodes of occlusion of the second shunt, the patient returned to the hospital with increasing ascites and respiratory distress related to ascites volume. Initial evaluation of the occluded shunt was performed with the technique described previously by several authors (1,9,10). Five microcuries of technetium-99m macroaggregates of albumin (MAA) were injected intraperitoneally, and gamma camera images of the abdomen and chest were obtained. The patient was supervised during pumping of the valve chamber. Failure to visualize the shunt itself, or absence of activity within the lungs within 2 hours, was considered evidence of shunt occlusion (Fig 2). In each instance, angiography (with digital subtraction [n = 21 or conventional [n = 11 technique) (Fig 3) was then performed to directly visualize the shunt tubing and pump chamber. Puncture of the proximal (abdominal) limb at its site of insertion into the pump chamber, as well as the distal (venous) limbipump chamber, was carried out with a 25-gauge butterfly needle. Ionic contrast media (Reno-M-60; Squibb, New Brunswick, NJ) was injected by hand under fluoroscopic con-
136
Journal of Vascular and Interventional Radiology
February 1992
venous CamIDIWI)
RsdiOpaqM
mlw
Second one-Way vdve Pump Chamber
FlmOne-Way valve
S u mPad
Fenemled Pentooel catheter (~roxqma1
a. b. Figure 1. (a)Line drawings of double-valve (left) and single-valve (right) Denver peritoneovenous shunts. (b) Close-up photograph of the valve section of a double-valve Denver shunt. Note the dual miter valves with direction-of-flow arrow demonstrating the unidirectional nature of the valves. (Photo and drawings courtesy of Denver Biomaterials, Evergreen, Colo). trol in all cases. Attempts were made to visualize both limbs of the shunts as well as the pump chamber. Fibrinolysis was accomplished by using drip-infused urokinase (5,000 IUI mL). Dosages ranged from 100,000 to 250,000 IU administered at a rate of 8 mL/h. Prothrombin time (PT), partial thromboplastin time (PTT), and fibrinogen levels were determined prior to and at the termination of urokinase infusion. Therapy was monitored by means of multiple repeat contrast material injections made at 10-minute intervals. Therapeutic endpoint was considered reached when all three shunt portions were free of obstruction (Fig 4) and free flow of contrast material was seen intraperitoneally and intravenously. One episode revealed the shunt to be encased in a tubular fibrinous sheath (Fig 5), a common occurrence known to cause shunt occlusion and failure.
strate contrast material within either the proximal or distal tubing. The first study revealed the shunt to be encased in a fibrinous sheath. Although lysis was achieved within the shunt, surgical revision was required to remove the sheath. After lysis in the second and third episodes, contrast material was noted exiting freely into the peritoneal cavity and central venous system and circulating through the pump chamber. Following the first two procedures, the patient's condition improved and she was discharged from the hospital. The third time, lysis was followed by onset of disseminated intravascular coagulopathy (DIC) and death from multiple organ hemorrhages 24 hours after discontinuance of the urokinase infusion. Autopsy revealed the shunt to be free of clot and debris. No pulmonary emboli or central venous thrombi were found; the pathologist attributed the DIC to the rapid central venous bolus of ascites following shunt lysis, not to the urokinase infusion.
Figure 2. Image obtained 30 minutes after intraperitoneal injection of Tc-99m MAA. The two markers show location of the pump assembly. Note the lack of lung activity signifying nonfunction of the shunt.
:D CVP
OCCLIJOEO PERI'TONER1
RESULTS Lysis of the occlusive material in the shunt was observed in all three instances. Initial contrast material injections in all three instances of shunt failure demonstrated thrombus within the pump chamber and failed to demon-
DISCUSSION Peritoneovenous shunting has been performed to relieve benign and malignant ascites. Edney et al studied both LeVeen and Denver shunts in patients
Figure 3. Digital subtraction image shows contrast material in the pump chamber but none in either limb. This shunt had an occlusion of both distal central venous (cup ) and proximal (peritoneal) limbs.
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Figure 5. Conventional radiograph shows contrast material filling a perishunt fibrous sheath (open arrows) following extravasation around the proximal tubing puncture site (curved arrow). Fibrous sheaths are common occurrences and may lead to shunt occlusion and malfunction. Straight solid arrow indicates proximal (peritoneal)limb.
Figure 4. Digital subtraction image obtained after infusion of urokinase. Contrast material can now be seen in both proximal and distal limbs.
in whom conventional medical therapy (diuretics, fluid restrictions) and repeated paracentesis had failed (2). All of their patients developed laboratory evidence of DIC (as evidenced by increase in fibrin split products [FSPs], PT, and PTT, decreased clotting factors, fibrinogen level, and platelet count) (111, with a single case of clinical DIC. They found no difference between occlusion rates of the two shunt types. Shunt life did vary with malignant ascites depending on the tumor type, suggesting that shunt malfunction was related to ascites composition (ie, cellularity, viscosity). Other authors studying the causes of shunt malfunction grouped them into several categories: thrombosis of the valve chamber, catheter, or vein; inflow failure from viscous ascites, cellular debris, fibrin aggregates, or catheter loculation (1,9,12,13);increased central venous pressure (14); or patient noncompliance (15). Other causes of shunt failure included infection, catheter malposition (including engulfment of the
catheter by the omentum) or migration (3) of the venous limb to either an extravascular or an improper intravascular position, intractable congestive heart failure requiring shunt ligation (from ascites inflow into the central venous system), and DIC (2,lO) as well as a single episode of tumor embolus (16). One author suggested that despite increased risks of hypoalbuminemia, infection, and discomfort, repeated paracentesis, rather than shunting, should be performed in patients with acute onset of large-volume ascites and life expectancies of less than 1month. He suggested that peritoneovenous shunting be reserved for patients with slowly accumulating ascites and longer life expectancies (12). DIC associated with peritoneovenous shunting has been studied by several authors. Early investigators attributed the DIC (occurring in 20%-100% of patients with shunts [17]) to dose-related ascitic inflow but did not isolate the specific factor(s) responsible. Relative thrombocytopenia, decreased plasma levels of antithrombin 111, plasminogen, antiplasmin, factors V and VIII, as well as a hemodilutional de-
crease in platelet count, are usually seen as early as the first postoperative day (18). Elevated FSPs may be due to both infused ascitic FSPs as well as split products from the DIC itself (11). Agents postulated to induce DIC include a procoagulant "activity" within the cellular component of the ascites (19,201 and, more recently, a plasminogen activator of peritoneal tissue origin (18). FSPs in the ascitic fluid (from rapid lysis of intraascitic fibrin) have also been indicated as a possible mediator. As opposed to malignant ascites, ascites from cirrhosis and chronic renal failure (nephrogenic ascites) is usually acellular and of low viscosity (21). Shunt failure in cirrhotic patients is usually due to thrombus in the shunt tube and valve chamber. Following manual pump activation in early Denver shunts, a small venous backflow was observed to fill the unit with blood. Slow clearance of this blood led to thrombosis (22). It was this regurgitation that led the makers of the Denver shunt to install a second, distal valve in the pump chamber. Single-valve shunts currently are recommended only for extremely viscous ascites (18). Postcompression reexpansion of the pump chamber would be accompanied by further aspiration of ascites, rather than retrograde inflow of blood from the venous limb. Shunts with several different flow rates were also developed to help decrease rapid delivery of fl uid boluses into the central venous system and thereby reduce the incidence of DIC and congestive heart failure (14). Placement of the venous limb was also noted to affect duration of function. Gleysteen and Klamer reported greater shunt longevity when the venous tubing terminated in the right atrium than in the superior vena cava or subclavian
138
Journal of Vascular and Interventional Radiology
vein and attributed the observation to an increase in pericatheter flow (11). Peritoneovenous shunt placement in patients with nephrogenic ascites is a last resort procedure, following failure of medical therapy. Hobar et a1 found shunts helped alleviate hemodialysisinduced hypotension and hypoalbuminemia, increased patients' appetites, and allowed greater patient activity. No shunt-induced deaths were noted, and failures were due to thrombosis and catheter migration (6). Review of the literature pertaining to lysis of long-term intravenous catheters (23-28) and extravascular, intracavitary fibrinous collections (29,30), as well as our experience with urokinasemediated thrombolysis in failed synthetic vascular grafts, led us to the present application of urokinase for shunt salvage in our patient with nonmalignant ascites. Review of 15 years of medical literature (29 articles) revealed a single report of urokinase-mediated thrombolysis for failed Denver shunts, but other surgical and nonsurgical methods were proposed (31). Only Balon and Fink-Bennett mentioned urokinase in her description of restoration of Denver shunt patency (10). Our patient had undergone numerous operations for dialysis graft revision and placement of acute dialysis central venous catheters. It was for this reason that we endeavored to avoid additional surgery in the hope of improving the patient's quality of life. Multiple surgeries place the patient at increased risk of anesthesia- and surgery-related morbidity and mortality (of increased concern in patients with hepatic dysfunction), wound infection, and eventual central venous access fibrosis, stenosis, and occlusion. Preservation of venous access is important in dialysis patients who may require multiple shunt sites and temporary central venous dialysis catheters throughout their lives. Thrombolysis is a treatment alternative offering a short hospital stay and potentially lower cost than surgery. Our patient died of overwhelming DIC 24 hours after our third treatment in 2 years. Autopsy revealed a thrombus-free shunt lumen. I t was the opinion of the patient's physician and the
clinical pathologist that the DIC was caused by a rapid ingress of ascites into the central venous system. The dosage of urokinase administered (approximately 250,000 IU), coagulation studies grossly within normal limits following therapy (PT, 14.2 seconds; normal, 19.0-23.0 seconds; PTT, 39.2 seconds; normal, 23.0-40.0 seconds), and the short half-life of urokinase (15 minutes), provided ample evidence that there was no relationship between the urokinase per se and the DIC that developed. Although the rapid influx of ascites could have been anticipated, no method of preventing its flow or retarding its rate was initiated. Ascites flow rates are related to the opening pressures of the miter valves and to the manufacturer's design parameters. Two flow rate styles are available in both the single- and double-valve designs. A decrease in intraabdominal pressure (and therefore decreased transshunt flow) could possibly have been obtained with paracentesis before initiation of lytic therapy. In summary, we have demonstrated the utility of urokinase in the salvage of a thrombosed, nonfunctional Denver shunt in a patient with nonmalignant ascites. Modifications to the Denver shunt and better patient compliance may decrease the frequency of shunt failure due to thrombus but not decrease occlusion due to fibrin clumps. Our experience suggests that urokinase therapy for occluded Denver shunts may be useful in cases of nephrogenic and cirrhotic ascites. References 1. Roussel JG, Kroom BB, Hart GA. The Denver type for peritoneovenous shunting of malignant ascites. Surg Gynecol Obstet 1986; 162:235240. 2. Edney JA, Hill A, Armstrong D. Peritoneovenous shunts palliate malignant ascites. Am J Surg 1989; 158:598-601. 3. Moritz MJ, Hoch JR, Rosato FE. Simple revision of the Denver peritoneovenous shunt with nonfunction from inflow occlusion. Surg Gynecol Obstet 1987; 165:71-72. 4. Smith DA, Weaver DW, Bouwman DL. Peritoneovenous shunt (PVS)
for malignant ascites. Am Surg 1989; 55:445-449. Sheth NK, Gleysteen JJ. Infiltrative fibrosis with acute hemorrhagic intestinal infarction: association with a peritoneovenous shunt. Surgery 1986; 100:99-104. Hobar PC, Turner WW, Valentine RJ. Successful use of the Denver peritoneovenousshunt in patients with nephrogenic ascites. Surgery 1987; 101:161-164. Soderlund C. Denver peritoneovenous shunting for malignant or cirrhotic ascites. Scand J Gastroenterol 1986; 21:1161-1172. Guzman E, Wigness B, Dorman F, et al. Advances and new concepts in the designing of peritoneovenous shunts for the treatment of refractory ascites. Trans Am Soc Artif Intern Organs 1988; 34:805-807. Fulenwider JT, Galambos JD, Smith RB, et al. LeVeen versus Denver peritoneovenous shunts for intractable ascites of cirrhosis. Arch Surg 1986; 121:351-355. Balon H, Fink-Bennett D. Scintigraphic demonstration of restored Denver peritoneovenous shunt patency using urokinase. Clin Nucl Med 1989; 14:310-311. Gleysteen J J , Klamer TW. Peritoneovenous shunts: predictive factors of early treatment failure. Am J Gastroenterol1984; 79:654-658. Turner WW. Chylous ascites: resolution after Denver peritoneovenous shunt. South Med J 1983; 76:539. Li MK, Shiu W, Li AK. The use of double valve Denver peritoneal venous shunt for malignant ascites. Ann Acad Med Singapore 1988; 17: 129-131. Li KW, Wong WS. Double valve Denver peritoneal venous shunt used in ovarian malignant ascites: a case report. Chin Med J 1989; 102: 300-302. Newkirk JB. Single-valvevs double-valve Denver peritoneovenous shunts for ascitic fluid (letter).Arch Surg 1987; 122:619. Akimaru, K, Ueda Y, Shoji T. Peritoneovenous shunting for intractable cirrhotic and cancerous ascites using different types of shunting tubes. Jpn J Surg 1988; 18:502-508. Millard FC, Powis SJ. Management of intractable malignant ascites using the Denver peritone-
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18.
19.
20.
21.
ovenous shunt. J R Coll Surg Edinb 1988; 33:138-139. Fildes J , Narvaez GP, Baig KA, et al. Pulmonary tumor embolization after peritoneovenous shunting for malignant ascites. Cancer 1988; 61: 1973-1976. Sonnenfeld T, Tyden G. Peritoneovenous shunts for malignant ascites. Acta Chir Scand 1986; 152: 117-121. Harmon DC, Demirjian A, Ellman L, et al. Disseminated intravascular coagulation with the peritoneovenous shunt. Ann Intern Med 1979; 90:774-776. Giannone G, Glabman S, Burrows L, et. al. Treatment of refractory ascites in hemodialysis patient with peritoneovenous shunt (Denver shunt). Mt Sinai J Med 1983; 50: 256-257.
22. McDaniel MD, Lewis TH. Nonsurgical relief of venous limb thrombosis in a Denver shunt (letter). JAMA 1984; 252:1282-1283. 23. Haire WD, Lieberman RP, Lund GB, et al. Obstructed central venous catheters. Cancer 1990; 66:22792285. 24. Monturo CA, Dickerson RN, Mullen JL. Efficacy of thrombolytic therapy for occlusion of long-term catheters. JPEN J Parenter Enteral Nutr 1990; 14:312-314. 25. Hurtubise MR, Bottino JC, Lawson M, et al. Restoring patency of occluded central venous catheters. Arch Surg 1980; 115:212-213. 26. Tschirhart JM,Rao MK. Mechanism and management of persistant withdrawal occlusion. Am Surg 1988; 54:326-328. 27. Moulton JS, Moore PT, Mencini RA. Treatment of loculated pleural effu-
28.
29.
30.
31.
sions with transcatheter intracavitary urokinase. AJR 1989; 153:941945. Vogelzang RL, Tobin RS, Burstein S, et al. Transcatheter intracavitary fibrinolysis of infected extravascular hematomas. AJR 1987; 148: 378-380. Gleysteen J , Hussey C, Heckman M. The cause of coagulopathy after peritoneovenous shunt for malignant ascites. Arch Surg 1990; 125: 474-477. Schwartz ML, Swaim WR, Vogel SB. Coagulopathy following peritoneovenous shunting. Surgery 1979; 85: 671-676. Ragni MV,Lewis JH, Spero JA. Ascites-induced LeVeen shunt coagulopathy. Ann Surg 1983; 198:9195.
Case Report
Fibrinolytic Therapy in a Patient with Denver Peritoneovenous Shunt Occlusion1 Neil J. Halin, DO Lewis M. Halin, DO
Index terms: Ascites, 791.77 Shunts, peritoneovenous, 95,4539,982,4539 Thrombolysis Urokinase
Urokinase thrombolytic therapy was used on three separate occasions to lyse thrombosed Denver peritoneovenous shunts in a 51-year-old woman. Shunt patency was preserved over a 2-yearperiod, with a fatal complicationfollowing the third procedure. The authors suggest that thrombolytic therapy might be a viable alternative to immediate surgical revision in patients with failed Denver shunts.
JVIR 1992; 3:135-139 Abbreviations: DIC = disseminated intravascular coagulopathy, FSP = fibrin split product, MAA = macroaggregates of albumin, PT = prothrombin time, PTT = partial thromboplastin time
' From the Department of Radiology, Metropolitan Hospital-Central Division, Philadelphia. Received May 17, 1991; revision requested June 20; revision received August 12; accepted August 22. Address reprint requests to N.J.H., 155 Dale St, Dedham, MA 02026. SCVIR, 1992
T H E use of peritoneovenous shunting of ascites with a manmade device was pioneered by Smith in 1962. Using a modified Spitz-Holter hydrocephalus drain, he proved peritoneocaval shunting was possible (1). The LeVeen shunt, a rigid plastic chamber housing a pressure-sensitive, one-way valve, was introduced in 1974 as the first job-specific peritoneovenous shunt. The Denvertype peritoneovenous shunt was introduced in 1979 and features a flexible pumping chamber and single-miter valve (2) (Fig 1).The valve opens at a positive pressure of 1cm of water and closes rapidly to prevent retrograde flow. Crystalline heparin is bonded to the lumen of the tubing and valve to help prevent thrombus formation. Since their introduction, the LeVeen and Denver shunts have been applied to the management of ascites due to various causes (3-8). Shunt failure and failure of surgically revised shunts due to occlusion are known to occur. Shunt occlusion in nonmalignant ascites may be due to fibrin aggregates or frank luminal thrombus formation. Both of these should be amenable to fibrinolysis or thrombolysis. Here, we present results of three episodes of nonsurgical shunt salvage in a single patient with use of the fibrinolytic drug urokinase (Abbokinase; Abbott Laboratories, North Chicago, Ill).
CASE REPORT Three occurrences of Denver shunt occlusion were treated in a 51-year-old
woman over a 2-year period. A singlevalve Denver peritoneovenous shunt (Denver Biomaterials, Evergreen, Colo) was placed in the patient for relief of ascites secondary to cirrhosis and chronic renal failure requiring hemodialysis. Following successful fibrinolysis, the first shunt became dislodged from the central venous system and a second shunt was placed. After each of two episodes of occlusion of the second shunt, the patient returned to the hospital with increasing ascites and respiratory distress related to ascites volume. Initial evaluation of the occluded shunt was performed with the technique described previously by several authors (1,9,10). Five microcuries of technetium-99m macroaggregates of albumin (MAA) were injected intraperitoneally, and gamma camera images of the abdomen and chest were obtained. The patient was supervised during pumping of the valve chamber. Failure to visualize the shunt itself, or absence of activity within the lungs within 2 hours, was considered evidence of shunt occlusion (Fig 2). In each instance, angiography (with digital subtraction [n = 21 or conventional [n = 11 technique) (Fig 3) was then performed to directly visualize the shunt tubing and pump chamber. Puncture of the proximal (abdominal) limb at its site of insertion into the pump chamber, as well as the distal (venous) limbipump chamber, was carried out with a 25-gauge butterfly needle. Ionic contrast media (Reno-M-60; Squibb, New Brunswick, NJ) was injected by hand under fluoroscopic con-
136
Journal of Vascular and Interventional Radiology
February 1992
venous CamIDIWI)
RsdiOpaqM
mlw
Second one-Way vdve Pump Chamber
FlmOne-Way valve
S u mPad
Fenemled Pentooel catheter (~roxqma1
a. b. Figure 1. (a)Line drawings of double-valve (left) and single-valve (right) Denver peritoneovenous shunts. (b) Close-up photograph of the valve section of a double-valve Denver shunt. Note the dual miter valves with direction-of-flow arrow demonstrating the unidirectional nature of the valves. (Photo and drawings courtesy of Denver Biomaterials, Evergreen, Colo). trol in all cases. Attempts were made to visualize both limbs of the shunts as well as the pump chamber. Fibrinolysis was accomplished by using drip-infused urokinase (5,000 IUI mL). Dosages ranged from 100,000 to 250,000 IU administered at a rate of 8 mL/h. Prothrombin time (PT), partial thromboplastin time (PTT), and fibrinogen levels were determined prior to and at the termination of urokinase infusion. Therapy was monitored by means of multiple repeat contrast material injections made at 10-minute intervals. Therapeutic endpoint was considered reached when all three shunt portions were free of obstruction (Fig 4) and free flow of contrast material was seen intraperitoneally and intravenously. One episode revealed the shunt to be encased in a tubular fibrinous sheath (Fig 5), a common occurrence known to cause shunt occlusion and failure.
strate contrast material within either the proximal or distal tubing. The first study revealed the shunt to be encased in a fibrinous sheath. Although lysis was achieved within the shunt, surgical revision was required to remove the sheath. After lysis in the second and third episodes, contrast material was noted exiting freely into the peritoneal cavity and central venous system and circulating through the pump chamber. Following the first two procedures, the patient's condition improved and she was discharged from the hospital. The third time, lysis was followed by onset of disseminated intravascular coagulopathy (DIC) and death from multiple organ hemorrhages 24 hours after discontinuance of the urokinase infusion. Autopsy revealed the shunt to be free of clot and debris. No pulmonary emboli or central venous thrombi were found; the pathologist attributed the DIC to the rapid central venous bolus of ascites following shunt lysis, not to the urokinase infusion.
Figure 2. Image obtained 30 minutes after intraperitoneal injection of Tc-99m MAA. The two markers show location of the pump assembly. Note the lack of lung activity signifying nonfunction of the shunt.
:D CVP
OCCLIJOEO PERI'TONER1
RESULTS Lysis of the occlusive material in the shunt was observed in all three instances. Initial contrast material injections in all three instances of shunt failure demonstrated thrombus within the pump chamber and failed to demon-
DISCUSSION Peritoneovenous shunting has been performed to relieve benign and malignant ascites. Edney et al studied both LeVeen and Denver shunts in patients
Figure 3. Digital subtraction image shows contrast material in the pump chamber but none in either limb. This shunt had an occlusion of both distal central venous (cup ) and proximal (peritoneal) limbs.
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Figure 5. Conventional radiograph shows contrast material filling a perishunt fibrous sheath (open arrows) following extravasation around the proximal tubing puncture site (curved arrow). Fibrous sheaths are common occurrences and may lead to shunt occlusion and malfunction. Straight solid arrow indicates proximal (peritoneal)limb.
Figure 4. Digital subtraction image obtained after infusion of urokinase. Contrast material can now be seen in both proximal and distal limbs.
in whom conventional medical therapy (diuretics, fluid restrictions) and repeated paracentesis had failed (2). All of their patients developed laboratory evidence of DIC (as evidenced by increase in fibrin split products [FSPs], PT, and PTT, decreased clotting factors, fibrinogen level, and platelet count) (111, with a single case of clinical DIC. They found no difference between occlusion rates of the two shunt types. Shunt life did vary with malignant ascites depending on the tumor type, suggesting that shunt malfunction was related to ascites composition (ie, cellularity, viscosity). Other authors studying the causes of shunt malfunction grouped them into several categories: thrombosis of the valve chamber, catheter, or vein; inflow failure from viscous ascites, cellular debris, fibrin aggregates, or catheter loculation (1,9,12,13);increased central venous pressure (14); or patient noncompliance (15). Other causes of shunt failure included infection, catheter malposition (including engulfment of the
catheter by the omentum) or migration (3) of the venous limb to either an extravascular or an improper intravascular position, intractable congestive heart failure requiring shunt ligation (from ascites inflow into the central venous system), and DIC (2,lO) as well as a single episode of tumor embolus (16). One author suggested that despite increased risks of hypoalbuminemia, infection, and discomfort, repeated paracentesis, rather than shunting, should be performed in patients with acute onset of large-volume ascites and life expectancies of less than 1month. He suggested that peritoneovenous shunting be reserved for patients with slowly accumulating ascites and longer life expectancies (12). DIC associated with peritoneovenous shunting has been studied by several authors. Early investigators attributed the DIC (occurring in 20%-100% of patients with shunts [17]) to dose-related ascitic inflow but did not isolate the specific factor(s) responsible. Relative thrombocytopenia, decreased plasma levels of antithrombin 111, plasminogen, antiplasmin, factors V and VIII, as well as a hemodilutional de-
crease in platelet count, are usually seen as early as the first postoperative day (18). Elevated FSPs may be due to both infused ascitic FSPs as well as split products from the DIC itself (11). Agents postulated to induce DIC include a procoagulant "activity" within the cellular component of the ascites (19,201 and, more recently, a plasminogen activator of peritoneal tissue origin (18). FSPs in the ascitic fluid (from rapid lysis of intraascitic fibrin) have also been indicated as a possible mediator. As opposed to malignant ascites, ascites from cirrhosis and chronic renal failure (nephrogenic ascites) is usually acellular and of low viscosity (21). Shunt failure in cirrhotic patients is usually due to thrombus in the shunt tube and valve chamber. Following manual pump activation in early Denver shunts, a small venous backflow was observed to fill the unit with blood. Slow clearance of this blood led to thrombosis (22). It was this regurgitation that led the makers of the Denver shunt to install a second, distal valve in the pump chamber. Single-valve shunts currently are recommended only for extremely viscous ascites (18). Postcompression reexpansion of the pump chamber would be accompanied by further aspiration of ascites, rather than retrograde inflow of blood from the venous limb. Shunts with several different flow rates were also developed to help decrease rapid delivery of fl uid boluses into the central venous system and thereby reduce the incidence of DIC and congestive heart failure (14). Placement of the venous limb was also noted to affect duration of function. Gleysteen and Klamer reported greater shunt longevity when the venous tubing terminated in the right atrium than in the superior vena cava or subclavian
138
Journal of Vascular and Interventional Radiology
vein and attributed the observation to an increase in pericatheter flow (11). Peritoneovenous shunt placement in patients with nephrogenic ascites is a last resort procedure, following failure of medical therapy. Hobar et a1 found shunts helped alleviate hemodialysisinduced hypotension and hypoalbuminemia, increased patients' appetites, and allowed greater patient activity. No shunt-induced deaths were noted, and failures were due to thrombosis and catheter migration (6). Review of the literature pertaining to lysis of long-term intravenous catheters (23-28) and extravascular, intracavitary fibrinous collections (29,30), as well as our experience with urokinasemediated thrombolysis in failed synthetic vascular grafts, led us to the present application of urokinase for shunt salvage in our patient with nonmalignant ascites. Review of 15 years of medical literature (29 articles) revealed a single report of urokinase-mediated thrombolysis for failed Denver shunts, but other surgical and nonsurgical methods were proposed (31). Only Balon and Fink-Bennett mentioned urokinase in her description of restoration of Denver shunt patency (10). Our patient had undergone numerous operations for dialysis graft revision and placement of acute dialysis central venous catheters. It was for this reason that we endeavored to avoid additional surgery in the hope of improving the patient's quality of life. Multiple surgeries place the patient at increased risk of anesthesia- and surgery-related morbidity and mortality (of increased concern in patients with hepatic dysfunction), wound infection, and eventual central venous access fibrosis, stenosis, and occlusion. Preservation of venous access is important in dialysis patients who may require multiple shunt sites and temporary central venous dialysis catheters throughout their lives. Thrombolysis is a treatment alternative offering a short hospital stay and potentially lower cost than surgery. Our patient died of overwhelming DIC 24 hours after our third treatment in 2 years. Autopsy revealed a thrombus-free shunt lumen. I t was the opinion of the patient's physician and the
clinical pathologist that the DIC was caused by a rapid ingress of ascites into the central venous system. The dosage of urokinase administered (approximately 250,000 IU), coagulation studies grossly within normal limits following therapy (PT, 14.2 seconds; normal, 19.0-23.0 seconds; PTT, 39.2 seconds; normal, 23.0-40.0 seconds), and the short half-life of urokinase (15 minutes), provided ample evidence that there was no relationship between the urokinase per se and the DIC that developed. Although the rapid influx of ascites could have been anticipated, no method of preventing its flow or retarding its rate was initiated. Ascites flow rates are related to the opening pressures of the miter valves and to the manufacturer's design parameters. Two flow rate styles are available in both the single- and double-valve designs. A decrease in intraabdominal pressure (and therefore decreased transshunt flow) could possibly have been obtained with paracentesis before initiation of lytic therapy. In summary, we have demonstrated the utility of urokinase in the salvage of a thrombosed, nonfunctional Denver shunt in a patient with nonmalignant ascites. Modifications to the Denver shunt and better patient compliance may decrease the frequency of shunt failure due to thrombus but not decrease occlusion due to fibrin clumps. Our experience suggests that urokinase therapy for occluded Denver shunts may be useful in cases of nephrogenic and cirrhotic ascites. References 1. Roussel JG, Kroom BB, Hart GA. The Denver type for peritoneovenous shunting of malignant ascites. Surg Gynecol Obstet 1986; 162:235240. 2. Edney JA, Hill A, Armstrong D. Peritoneovenous shunts palliate malignant ascites. Am J Surg 1989; 158:598-601. 3. Moritz MJ, Hoch JR, Rosato FE. Simple revision of the Denver peritoneovenous shunt with nonfunction from inflow occlusion. Surg Gynecol Obstet 1987; 165:71-72. 4. Smith DA, Weaver DW, Bouwman DL. Peritoneovenous shunt (PVS)
for malignant ascites. Am Surg 1989; 55:445-449. Sheth NK, Gleysteen JJ. Infiltrative fibrosis with acute hemorrhagic intestinal infarction: association with a peritoneovenous shunt. Surgery 1986; 100:99-104. Hobar PC, Turner WW, Valentine RJ. Successful use of the Denver peritoneovenousshunt in patients with nephrogenic ascites. Surgery 1987; 101:161-164. Soderlund C. Denver peritoneovenous shunting for malignant or cirrhotic ascites. Scand J Gastroenterol 1986; 21:1161-1172. Guzman E, Wigness B, Dorman F, et al. Advances and new concepts in the designing of peritoneovenous shunts for the treatment of refractory ascites. Trans Am Soc Artif Intern Organs 1988; 34:805-807. Fulenwider JT, Galambos JD, Smith RB, et al. LeVeen versus Denver peritoneovenous shunts for intractable ascites of cirrhosis. Arch Surg 1986; 121:351-355. Balon H, Fink-Bennett D. Scintigraphic demonstration of restored Denver peritoneovenous shunt patency using urokinase. Clin Nucl Med 1989; 14:310-311. Gleysteen J J , Klamer TW. Peritoneovenous shunts: predictive factors of early treatment failure. Am J Gastroenterol1984; 79:654-658. Turner WW. Chylous ascites: resolution after Denver peritoneovenous shunt. South Med J 1983; 76:539. Li MK, Shiu W, Li AK. The use of double valve Denver peritoneal venous shunt for malignant ascites. Ann Acad Med Singapore 1988; 17: 129-131. Li KW, Wong WS. Double valve Denver peritoneal venous shunt used in ovarian malignant ascites: a case report. Chin Med J 1989; 102: 300-302. Newkirk JB. Single-valvevs double-valve Denver peritoneovenous shunts for ascitic fluid (letter).Arch Surg 1987; 122:619. Akimaru, K, Ueda Y, Shoji T. Peritoneovenous shunting for intractable cirrhotic and cancerous ascites using different types of shunting tubes. Jpn J Surg 1988; 18:502-508. Millard FC, Powis SJ. Management of intractable malignant ascites using the Denver peritone-
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ovenous shunt. J R Coll Surg Edinb 1988; 33:138-139. Fildes J , Narvaez GP, Baig KA, et al. Pulmonary tumor embolization after peritoneovenous shunting for malignant ascites. Cancer 1988; 61: 1973-1976. Sonnenfeld T, Tyden G. Peritoneovenous shunts for malignant ascites. Acta Chir Scand 1986; 152: 117-121. Harmon DC, Demirjian A, Ellman L, et al. Disseminated intravascular coagulation with the peritoneovenous shunt. Ann Intern Med 1979; 90:774-776. Giannone G, Glabman S, Burrows L, et. al. Treatment of refractory ascites in hemodialysis patient with peritoneovenous shunt (Denver shunt). Mt Sinai J Med 1983; 50: 256-257.
22. McDaniel MD, Lewis TH. Nonsurgical relief of venous limb thrombosis in a Denver shunt (letter). JAMA 1984; 252:1282-1283. 23. Haire WD, Lieberman RP, Lund GB, et al. Obstructed central venous catheters. Cancer 1990; 66:22792285. 24. Monturo CA, Dickerson RN, Mullen JL. Efficacy of thrombolytic therapy for occlusion of long-term catheters. JPEN J Parenter Enteral Nutr 1990; 14:312-314. 25. Hurtubise MR, Bottino JC, Lawson M, et al. Restoring patency of occluded central venous catheters. Arch Surg 1980; 115:212-213. 26. Tschirhart JM,Rao MK. Mechanism and management of persistant withdrawal occlusion. Am Surg 1988; 54:326-328. 27. Moulton JS, Moore PT, Mencini RA. Treatment of loculated pleural effu-
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sions with transcatheter intracavitary urokinase. AJR 1989; 153:941945. Vogelzang RL, Tobin RS, Burstein S, et al. Transcatheter intracavitary fibrinolysis of infected extravascular hematomas. AJR 1987; 148: 378-380. Gleysteen J , Hussey C, Heckman M. The cause of coagulopathy after peritoneovenous shunt for malignant ascites. Arch Surg 1990; 125: 474-477. Schwartz ML, Swaim WR, Vogel SB. Coagulopathy following peritoneovenous shunting. Surgery 1979; 85: 671-676. Ragni MV,Lewis JH, Spero JA. Ascites-induced LeVeen shunt coagulopathy. Ann Surg 1983; 198:9195.
