Mark W. Mewissen

Reteplase in the Treatment of Peripheral Arterial and Venous Occlusions: A Pilot Study

PURPOSE Reteplase, a truncated mutant of tissue plasminogen activator, has been used successfully in the treatment of acute coronary occlusion, but, heretofore, it has not been investigated in the setting of peripheral vascular occlusion. Reteplase is a potential recombinant thrombolytic agent that may offer an appropriate alternative to currently employed plasminogen activators. MATERIALS AND METHODS Over a 6-month period reteplase was used to treat peripheral vascular occlusions at five centers in the United States. The agent was used in peripheral arterial occlusion (n = 26, 70.3%) or venous occlusion (n = 11, 29.7%), in doses ranging from 0.5 to 2.0 U/h, infused directly into the thrombus. A lacing dose (4.3 +/- 0.9 U) was employed in 17 patients (45.9%), and 25 patients (67.6%) received concurrent heparin therapy in a subtherapeutic dose (n = 14, 37.8%) or as full therapeutic anticoagulation (n = 11, 29.7%). RESULTS The 26 patients with arterial occlusions received a total dose of reteplase that averaged 20.5 U +/- 5.3 (mean +/- SEM), ranging from 3.5 to 82 U. The duration of infusion was 19.3 hours +/- 2.4 with a range of 0.2-36 hours. Complete dissolution of the occluding thrombus was achieved in 23 patients (88.5%). Hemorrhagic complications developed in eight patients (30.8%) and were major in five patients (19.2%). No patient experienced intracranial bleeding. Although there was no association between the dose regimen and thrombolytic efficacy, bleeding complications appeared to be more frequent as the dose was increased from 0.5 to 2.0 U/h. The 11 patients treated for deep venous thrombi received an average of 32.6 U +/- 7.4 of reteplase, ranging from 6 to 75 U over a mean length of time of 31.1 hours +/- 7.3 (range, 4-84 hours). Complete dissolution of thrombus occurred in eight patients (72.7%). Hemorrhagic complications developed in three patients (27.3%) and one of the episodes was major (9.1%). No patient experienced intracranial hemorrhage. CONCLUSIONS Reteplase appears to be an acceptable alternative thrombolytic agent with a satisfactory safety and efficacy profile in the setting of peripheral arterial and venous occlusion. As such, it may provide an attractive alternative for the treatment of peripheral arterial and venous thrombotic occlusions. However, definitive conclusions must await the results of controlled comparisons of reteplase to other thrombolytic agents.

Percutaneous intraarterial thrombolysis in the treatment of thrombosis of lower extremity arterial reconstructions

Vascular grafts may be salvaged with thrombolytic therapy after acute occlusion as an alternative to balloon catheter thrombectomy. From October 1987 to May 1990, 15 arterial bypasses to the lower extremity (infrainguinal saphenous vein [n = 7] or expanded polytetrafluoroethylene [n = 6], and Dacron aortofemoral bifurcation graft limbs [n = 2]) were treated for 30 occulsions with intraarterial urokinase (390,000 IU to 5,808,000 IU) infused from 3 to 40 hours. The origins of 15 graft occlusions were morphologic defects (intimal hyperplasia with anastomotic or conduit stricture), pseudoaneurysm, or progression of disease distal to the graft. Two occlusions were attributed to coagulation disorders. A cause could not be identified for 13 occlusions. Patency was initially restored to all grafts with use of thrombolytic therapy, however, adjunctive surgical thrombectomy to remove persistent thrombus from the graft or outflow vessels was required after six thrombolytic infusions. One graft in the series could not be salvaged leading to below-knee amputation. Graft defects were corrected by balloon angioplasty (n = 7) or surgical revision of the conduit (n = 8). Five significant hemorrhagic complications occurred from the catheter insertion site requiring four emergent surgical procedures and resulting in the death of a fifth patient from a myocardial infarction. This technique allows chemical thrombectomy of branch arteries distal to the graft and inaccessible to a balloon embolectomy catheter, and permits diagnosis of abnormal graft morphology that may be the cause of the graft occlusion. Graft reocclusion can be expected if technical defects in the arterial reconstruction are not revised or hypercoagulable states are not treated.

Catheter-directed thrombolysis for lower extremity deep vein thrombosis

The elimination of the embolic potential of existing thrombus, the restoration of unobstructed flow, the prevention of further thrombosis, and the preservation of venous valve function are the ideal goals of therapy for acute deep vein thrombosis (DVT). Meeting these goals will not only prevent pulmonary embolism but will also minimize the long-term sequelae of venous hypertension and the development of postthrombotic syndrome (PTS). Treatment strategies aimed at eliminating or reducing the risk of PTS should focus on preserving valvular function and eliminating the risk of continued venous obstruction after acute DVT. Thrombolytic agents are an attractive form of early therapy because they have the ability to eliminate obstructive thrombus in the deep veins and should therefore help provide protection against PTS. The perceived benefits of early and rapid recanalization in preserving valve function has been the basis for the use of lytic therapy to treat acute DVT.

Intraarterial cisplatin infusion in the management of transitional cell carcinoma of the bladder

Thirty patients with bulky T3 or T4 transitional cell carcinoma of the bladder, clinically determined to be without nodal or distant metastases, were treated with a 48‐hour hypogastric artery infusion of cisplatin (CDDP) 75–150 mg/m2 1 month before tumor resection. Complications of the CDDP infusions were milder than those with intravenous (IV) infusion or rapid intraarterial (IA) infusion, although three lower extremity neuropathies were seen. The CDDP infusions reduced the primary bladder mass effectively, and seven of 16 cystectomy specimens were rendered PO. However, patient survival was clearly predicted by the nodal status. Of 15 T3‐4N+MO patients, 11 died at 15 ± 3 months. Methotrexate, vinblastine, doxorubicin, and cisplatin (M‐VAC) chemotherapy was given if residual transitional cell carcinoma was found after IA CDDP. Of 12 P3NOMO patients undergoing cystectomy, eight are alive with no evidence of disease (NED) at 28 ± 8 months and no patient has died of transitional cell carcinoma. IA CDDP can effectively reduce bulky bladder cancer masses, but has no demonstrable effect on survival in N+ disease. It appears that adjuvant IA CDDP favorably affects survival in T3NOMO transitional cell carcinoma of the bladder.

Impact of peripherally inserted central catheters on phlebitic complications of peripheral intravenous therapy in spinal cord injury patients.

We investigated the impact of peripherally inserted central catheter (PICC) placement in spinal cord injury patients at high risk for infusion phlebitis. The rate and etiology of phlebitis was investigated in two phases. During Phase I, peripheral IV cannulae and conventional central venous catheters (CVC) were used. During Phase II, patients identified to be at risk for phlebitis received PICCs. The number of peripheral IVs, CVCs and PICCs was tabulated for both phases of the study. Technical, infectious and thrombotic complications were studied prospectively for PICCs and retrospectively for CVCs. We found the rate of phlebitis was 16.5 percent and 2.4 percent for Phases I and II, respectively (p = 0.0002). Three infections occurred in 38 PICCs and one infection was documented in 13 conventional CVCs. The number of peripheral IVs and conventional CVCs was reduced significantly from Phase I to Phase II. No procedural complications, catheter sepsis or clinically apparent venous thrombosis occurred. In conclusion, PICCs reduced the rate of phlebitis thresholds with a low complication rate and reduced the use of peripheral IVs and conventional CVCs.

Hemodialysis Catheter Placement Directly into Occluded Central Vein Segments: A Technical Note

THE continually growing population of patients with end-stage renal disease has further increased the demand for long-term hemodialysis. In 1993, 157,000 people in the United States alone received longterm hemodialysis, according to U.S. Renal Data. Of those patients, approximately 8.9% underwent dialysis with use of a permanent central venous catheter (1). These figures do not include temporary dialysis catheters, and therefore, the role of catheter-mediated hemodialysis remains understated. In this population, the high incidence of central venous stenosis and occlusion poses a challenge for maintaining permanent hemodialysis access. Previously, a central venous stenosis or occlusion eliminated ipsilatera1 access sites and restricted the number of possible alternatives. Recanalization of central venous occlusions in such instances has recently been described in the literature and may provide extended access to previously occluded veins (2,3). We describe an alternative technique for central venous recanalization and successful implantation of a permanent hemodialysis catheter.

Postcontrast CT in the diagnosis and assessment of response to thrombolysis in massive pulmonary embolism.

We present a case of massive acute pulmonary embolism where contrast enhanced helical CT was compared with standard angiography for diagnosis and for monitoring subsequent response to thrombolytic therapy. There was very close concordance of the findings on these modalities suggesting that contrast enhanced helical CT may be an easy and reliable alternative to standard angiography.

Catheter-directed thrombolysis for the treatment of symptomatic lower extremity deep vein thrombosis

Inevitably, catheter-directed thrombolysis (CDT) techniques developed to treat native artery and graft thromboses were applied to symptomatic lower extremity deep vein thrombosis (DVT). Data from nearly 300 patients treated with CDT and enrolled in a venous registry were reviewed. Seventy percent of patients presented with iliofemoral DVT. Venous access was gained through the popliteal vein in 42% of patients and urokinase was administered via a coaxial infusing system in the majority of cases over a mean of 53.4 hours and a mean dose of 7.8 million units. Significant lysis (>50%) was achieved in 83%, complete lysis in 33%. Nearly 40% of patients required an iliac stent. Complications included major bleeding in 11.5%, and 2 deaths resulting from an intracranial hemorrhage and 1 pulmonary embolus. This experience shows that CDT can safely and effectively dissolve thrombus from deep veins of identifiable groups of patients with lower limb DVT.

Laser-Assisted Transgraft Embolization: A Technique for the Treatment of Type II Endoleaks

A transgraft embolization (TGE) technique was performed in a patient to treat a type II endoleak. Using a transfemoral arterial approach, the endograft was punctured using a coronary laser catheter aimed toward the type II endoleak nidus, which was treated with Onyx (Medtronic, Minneapolis, Minnesota). TGE resulted in successful embolization, as demonstrated on 1-year follow-up CT angiography, which showed complete elimination of the type II endoleak and shrinkage of the aneurysmal sac. TGE is an alternative to transarterial embolization, translumbar embolization, and transcaval embolization.

Arterial Duplex Surveillance of Implanted Nitinol Stents in the Femoropopliteal Segment for Relief of Lower Extremity Ischemia

Purpose To evaluate the role of duplex scanning as an imaging tool in surveillance of the natural history of femoropopliteal arterial segments treated with self-expandable nitinol stents. Methods From March 1999 to December 2001, 92 limbs in 84 patients were treated with self-expanding stents in the femoropopliteal (FP) segment for the relief of chronic limb ischemia. Follow-up studies included color duplex ultrasonography (CDU) and ankle/brachial indices (ABIs) in 57 limbs. Duplex criteria used to determine the presence of a significant in-stent stenosis was an increase in the peak systolic velocity within the stent of >100% from the proximal segment. The presence of a hemodynamically significant stenosis was then correlated with the concurrent ABI. Results Eleven in-stent stenoses were documented in 11 limbs. In those patients, the mean decrease in ABI was 0.29, ranging from 0.13 to 0.50. In 46 patients with a <50% stenosis identified on CDU, the mean change in ABI was by comparison not significant. Conclusions From these data, the degree of in-stent stenosis (>50%) by duplex ultrasonographic criteria correlates well with a significant stenosis within a stented segment of the femoropopliteal artery. It seems that CDU is an ideal noninvasive imaging tool to objectively surveillance stent patency.