Endovascular Therapies

Catheter directed techniques include procedures aimed at obliteration of the blood supply to a diseased tissue or organ, or the delivery of therapeutic agents in very high concentration to a diesased tissue through is blood supply. Endovascular therapies are often used as an adjunct to conventional medical and surgical treatments, but may also be used to definitively treat some abnormalities.

Embolization Procedures

Transcatheter techniques for devascularization are useful in a wide variety of diseases. The role of transcatheter embolization has expanded greatly in recent years with the availability of coaxial microcatheter systems that allow delivery of the embolic agent to the site of treatment with extreme precision.

Embolization is used primarily as a preoperative measure to minimize intraoperative blood loss, and as a primary therapy in arteriovenous malformations and hemangiomas. It is an important palliative therapy for metastatic disease in the liver, particularly for metastases from hormonally active tumors such as carcinoid. Embolization is also used to control bleeding from trauma, iatrogenic injury, malignancy, and from upper GI tract diseases. Transvenous embolization is used adjunctively with transjugular intrahepatic portosystemic shunts to control bleeding from esophageal varices, and as a definitive treatment for varicocele.

Embolization materials can be divided into 4 broad categories: particulates, mechanical occlusion devices, sclerosants, and liquid embolic agents. The most frequently used particulate embolic agents are gelfoam, microfibrillar collagen, and polyvinyl alcohol. Of these, gelfoam and microfibrillar collagen are considered to be temporary agents, while polyvinyl alcohol produces semi-permanent or permanent occlusion. Particulates work by occluding the precapillary arterioles and small arteries. Consequently, these agents are inappropriate where large arteriovenous communications exist, or where embolization is done directly into a vein.

Metallic coils and detachable balloons are frequently used to occlude larger vessels (arteries and veins). Coils are made of stainless steel or platinum, and most are coated with thrombogenic mylar filaments. Detachable balloons are made of latex, silicone or other conforming materials. These balloons are delivered on a catheter and inflated with either isotonic contrast medium or a slowly polymerizing liquid plastic. Following inflation, a valve at the balloon-catheter junction allows the catheter to detach leaving the inflated balloon in place.

Sclerosing agents constitute another class of embolization materials. Absolute ethanol is the most commonly used agent in this group. Ethanol acts by denaturing proteins in the endothelium of the microcirculation, resulting in complete thrombosis of the vascular bed. Sotradecol, sodium morrhuate, and boiling contrast medium are also used as sclerosants.

Lastly, there are liquid agents such as silicone rubber, Ethibloc (amino acid gel) and IBCA (isobutyl-2-cyanoacrylate "crazy glue") that act by solidifying shortly after exposure to an ionic environment. These agents work by forming a permanent cast of the vascular bed. Lipiodol (iodinated poppy seed oil) is a liquid agent that is immiscible with blood. Lipiodol droplets will occlude arterioles only temporarily. Therefore, as a pure embolic agent, lipiodol is of little or no practical value. However, lipiodol is subject to avid uptake by certain tumor cells, but not by cells of normal tissue. This property makes lipiodol useful when combined with chemotherapeutic agents for chemo-embolization.

In chemo-embolization, chemotherapeutic agents, most commonly 5FU, adriamycin, and mitomycin, are combined with embolic materials such as gelfoam, PVA, or lipiodol, and injected directly into the arterial supply of a tumor. Combining local injection of the chemotherapeutic agent with embolization results in a very high and sustained concentration of the drug at the site of disease with minimal systemic toxicity. Chemo-embolization has been used extensively in Asia for treatment of hepatoma, a common malignancy in that region. Studies from Japan comparing this form of treatment with systemic chemotherapy have shown chemo-embolization to significantly improve the survival of patients with hepatoma. In North America, hepatoma is rather rare and chemo-embolization is used most often for treatment of hepatic metastases, particularly those of colon carcinoma. Although chemo-embolization is extremely effective in reducing tumor burden, it is a local therapy and therefore unable to eradicate metastatic disease. Consequently, recurrence is common and this procedure, while palliative, does not appear to improve overall survival.

A careful and thorough angiographic work-up is essential prior to any embolization procedure. Embolization is generally not appropriate for lesions supplied by end-arteries unless the portions of the organ subserved by the target vascular territory can be sacrificed. For example, preoperative embolization of a bleeding carcinoma of the colon may be possible without infarcting bowel, while embolization of a bleeding colonic diverticulum or small vascular malformation carries a 20% risk of significant ischemia and bowel infarction. Very recently, small bowel and colonic bleeders have been successfully treated without significant complications using microembolization techniques. Similarly, cavernous hemangiomas and vascular malformations of the tongue and digits must be approached with extreme caution. These lesions are usually best treated by direct puncture with injection of a sclerosing agent into the abnormal vascular bed.

Intraarterial Infusion Therapy

Transcatheter intraarterial infusion therapy is a useful technique for the local delivery of pharmaceutical agents in a variety of clinical settings. These procedures are used most commonly for infusion of chemotherapeutic agents and vasoactive drugs.

Using selective catheterization and microcatheter techniques, chemotherapeutic agents can be infused directly into the arterial supply of a tumor. This results in a transient but very high concentration of the antineoplastic drug in the tumor, often with a lower total dose than would be given in systemic therapy. Consequently, the tumoricidal effects of the agent are enhanced while systemic toxicity is minimized. Intraarterial chemotherapy infusion differs from chemo-embolization (discussed in the previous section) in that the vascular bed of the tumor is not obliterated, thus preserving the opportunity for repeat treatment. Intraarterial chemotherapy infusion is usually a palliative procedure, although it has been used to reduce tumor size preoperatively.

Vasodilators such as papaverine or priscoline may be infused intraarterially to relieve mesenteric ischemia due to a low flow state (non-occlusive ischemia). Intraarterial papaverine has been used successfully in cerebral ischemia due to vasospasm following subarachnoid hemorrhage or craniotomy. Papaverine infusion has also been useful as a temporizing measure in limb threatening ischemia due to Raynaud's disease and other vasospastic conditions.

The most frequent use of intraarterial infusion therapy is for local administration of a vasoconstrictor to control acute gastrointestinal bleeding. This is a useful adjunct to emergency surgery. In some cases it provides definitive treatment, in others it provides temporary control of bleeding while the patient is stabilized and prepared for surgery. The agent most commonly used in these procedures is vasopressin (antidiuretic hormone).

Vasopressin is a posterior pituitary hormone without oxytocin activity. Other agents including epinephrine, prostaglandin F and glypressin have been used in the past, but have been less effective or had greater side effects. Vasopressin acts directly on smooth muscle producing both splanchnic vasoconstriction and contraction of the muscularis of the bowel. Vasopressin may be given intravenously or intraarterially. Intraarterial administration produces higher efficacy and a lower incidence of untoward effects such as generalized vasoconstriction, hypertension, cardiac ischemia and arrhythmias, and metabolic derangements with fluid overload and hyponatremia due to antidiuretic effects. Rarely, vasopressin therapy has resulted in bowel ischemia or infarction, or mesenteric venous infarction. The reported incidence of complications related to intraarterial vasopressin therapy is less than 7%. Effective control of bleeding is reported in 65 to 85% of cases. Vasopressin will be most effective when infused directly into the artery supplying the lesion. If selective catheter placement is not possible, vasopressin may be infused into the celiac, superior mesenteric, or inferior mesenteric artery origin.

Vasopressin is contraindicated in patients with clinically significant coronary artery disease, recent myocardial infarction, advanced cerebral vascular disease, advanced peripheral vascular disease, congestive heart failure, and renal failure with fluid retention. Vasopressin should be used with caution in patients with advanced liver disease and portal hypertension. In normal patients, infusion of vasopressin into the hepatic artery results in initial arterial constriction followed by hepatic artery escape (sometimes described as paradoxical hepatic vasodilatation). Portal venous input accounts for 60 to 75% of the total hepatic blood flow. However, this ratio is variable and homeostasis of total hepatic blood flow balances portal venous and hepatic arterial input in a reciprocal fashion. Thus, as portal venous input declines, vasodilatation occurs in the hepatic arteries. In severe portal hypertension, the effective portal venous input is very low and the hepatic arteries are maximally dilated. In these patients, infusion of a vasoconstrictor into the hepatic artery can produce a significant ischemic insult to the liver. A similar circumstance can occur where the hepatic artery is replaced to the superior mesenteric artery. In these individuals, vasopressin infusion into the origin of the SMA will reduce both portal and hepatic arterial flow. In most patients, splenic and inferior mesenteric venous flow will suffice until hepatic artery escape. However, patients with portal hypertension with or without portosystemic shunts, and patients with normal livers who have had a splenectomy are at risk for ischemic liver injury.

Vasopressin is most effective in treating mucosal lesions where the bleeding arises from capillaries and small arteries and veins. Effective control of bleeding ultimately relies on normal coagulation. Although patients with coagulopathy may be controlled during the infusion, these patients will not produce a satisfactory hemostatic plug and bleeding will recur when the infusion is stopped. Large arteries and abnormal vessels that do not have a muscular coat are poorly controlled. Thus, in the upper GI tract, erosive gastritis, duodenitis, and other superficial ulceration can be controlled, while peptic ulcers, and Mallory-Weiss tears may respond poorly to vasoconstrictor therapy. Vasopressin will have no effect in bleeding from a neoplasm, since neoplastic vessels lack a muscular coat and cannot respond to vasoconstrictors. In lower GI tract bleeding, vasopressin should be considered in nearly all patients bleeding from other than neoplastic lesions. Vasopressin will control bleeding in 90% of diverticula, with a 30% incidence of recurrence. Thus, more than 50% of these patients will be definitively treated by infusion therapy alone. Higher recurrence rates are seen in major angiodysplasias and arteriovenous malformations. Nevertheless, vasoconstrictor therapy is useful in these patients to gain immediate control of bleeding and allow the patient to be stabilized for elective surgery.

Once the bleeding site is localized and the decision to attempt pharmacological control is made, the catheter is placed selectively into the branch supplying the lesion. Vasopressin is diluted in normal saline or D5W at 100 IU vasopressin per 250 cc diluent (0.4 IU / cc) and the infusion is begun at 0.2 IU per minute (30 cc / hr) with an arterial infusion pump. Angiography is repeated after 20 minutes. If there is continued evidence of bleeding, the infusion is increased to 0.4 IU / minute (60 cc / hr) and angiography is repeated after another 20 minutes. If bleeding is still present, it is unlikely that further increases beyond 0.4 IU / minute will be effective and embolization or surgery should be considered.

When bleeding is controlled, the patient is sent to the ICU and monitored clinically for signs of recurrence. The infusion is continued for 12-24 hours and then decreased by 50% at 12-24 hour intervals until the rate is < 0.1 IU / minute. Following 12-24 hours infusion at <0.1 IU / minute, the vasopressin is stopped and D5W, NS or LR is infused for an additional 6-12 hours to maintain catheter patency. If there is no further evidence of bleeding, the catheter is removed.