HYPAQUE™ Sodium (Diatrizoate Sodium Injection, USP) 50%

Radiopaque diagnostic agents may be useful to investigate the presence and extent of certain malignancies such as: gliomas including malignant gliomas, glioblastomas, astrocytomas, oligodendrogliomas and gangliomas, ependymomas, medulloblastomas, meningiomas, neuromas, pinealomas, pituitary adenomas, craniopharyngiomas, germinomas, and metastatic lesions.

The usefulness of contrast enhancement for the investigation of the retrobulbar space and in cases of low grade or infiltrative glioma has not been demonstrated.

In calcified lesions, there is less likelihood of enhancement. Following therapy, tumors may show decreased or no enhancement.

The opacification of the inferior vermis following contrast media administration has resulted in false-positive diagnosis in a number of normal studies.

The use of injectable radiopaque diagnostic agents may be beneficial in the image enhancement of nonneoplastic lesions. Cerebral infarctions of recent onset may be better visualized with contrast enhancement, while some infarctions are obscured if contrast media are used. The use of iodinated contrast media results in contrast enhancement in about 60 percent of cerebral infarctions studied from one to four weeks from the onset of symptoms.

Sites of active infection may also be enhanced following contrast media administration.

Arteriovenous malformations and aneurysms will show contrast enhancement. For these vascular lesions, the enhancement is probably dependent on the iodine content of the circulating blood pool.

Hematomas and intraparenchymal bleeders seldom demonstrate any contrast enhancement. However, in cases of intraparenchymal clot, for which there is no obvious clinical explanation, contrast media administration may be helpful in ruling out the possibility of associated arteriovenous malformation.

Urography is contraindicated in patients with anuria.

See PRECAUTIONS—General. Some clinicians consider multiple myeloma a contraindication to excretory urography because of the great possibility of producing transient to fatal renal failure. Others believe that the risk of causing anuria is definite but small. If excretory urography is performed in the presence of multiple myeloma, dehydration should be avoided since it favors protein precipitation in renal tubules.

Although azotemia is not considered a contraindication, care is required in patients with advanced renal failure. The usual preparatory dehydration should be omitted, and urinary output should be observed for one to two days in these patients. Adequate visualization may be difficult or impossible to attain in patients with severely impaired renal and/or hepatic function. Use with extreme caution in patients with concomitant hepatorenal disease.

See ADVERSE REACTIONS—General.

Carotid angiography during the progressive period of a stroke should be avoided, particularly on the left side because of the increased risk of cerebral complications.

See PRECAUTIONS—General. Patients in whom cerebral angiography is to be performed should be selected with care.

Although cerebral angiography has been considered contraindicated in patients who have recently experienced cerebral embolism or thrombosis (stroke syndrome), many experts now believe that the diagnostic value of the procedure, when employed early as an aid in locating lesions amenable to operation, outweighs any added risk to the patient. Furthermore, a small number of postangiographic fatalities have been reported, including progressive thrombosis already clinically evident before angiography, in which the procedure did not appear to play any direct role. Patients with severe cerebrovascular disease should be examined primarily by indirect methods of angiography.

In cerebral angiography, every precaution must be taken to prevent untoward reactions. Reactions may vary directly with the concentration of the substance, the amount used, the speed and frequency of injections, and the interval between injections.

In subarachnoid hemorrhage, angiography is expected to be hazardous. In migraine, the procedure can be hazardous because of ischemic complications, particularly if performed during or soon after an attack.

See ADVERSE REACTIONS—General. With any contrast medium introduced into the cerebral vasculature, neurologic complications, including neuromuscular disorders, seizures, loss of consciousness, hemiplegia, unilateral dysesthesias, visual field defects, language disorders (aphasia), amnesia, and respiratory difficulties may occur, particularly when the extent of the intrinsic lesion is unknown. Such untoward reactions are for the most part temporary, although permanent visual field defects have been reported. Some investigators who are experienced in angiographic procedure emphasize the fact that they tend to occur after repeated injections or higher doses of the contrast medium. Other clinicians find that they occur most frequently in elderly patients. In as much as the procedure itself is attended by technical difficulties regardless of the risk the patient presents (eg, mechanical catheter obstruction of the vertebral artery can cause transient blindness), the more experienced the radiologic team, the fewer the complications of any degree that are apt to arise.

Amaurosis can occur following carotid or especially selective vertebral arteriography. It is almost always transitory (4 to 48 hours).

A dose of 8 mL to 12 mL injected at a rate not exceeding the normal flow in the carotid artery (about 5 mL per second) is suggested. The dose may be repeated as indicated; however, an increased risk attends each repeat injection. In the retrograde brachial or catheter method (aortic arch), a single injection of 35 mL to 50 mL is generally used. Children require a smaller dose in proportion to weight. Light anesthesia may be required in these procedures.

See PRECAUTIONS—General. Extreme caution is advised in considering peripheral arteriography in patients suspected of having thromboangiitis obliterans (Buerger’s disease) since any procedure (even insertion of a needle or catheter) may induce a severe arterial or venous spasm. Caution is also advisable in patients with severe ischemia associated with ascending infection.

See ADVERSE REACTIONS—General. Soreness in extremities has also been reported.

Adverse reactions observed during peripheral arteriography may sometimes be due to arterial trauma during the procedure (ie, insertion of needle or catheter, subintimal injection, perforation) as well as to the hypertonicity or effect of the medium. Reported adverse reactions include transient arterial spasm, extravasation, hemorrhage, hematoma formation with tamponade, injury to nerves in close proximity to artery, thrombosis, dissecting aneurysm, arteriovenous fistula (eg, with accidental perforation of femoral artery and vein during the needing), and transient leg pain from contraction of calf muscles in femoral arteriography. Transient hypotension has been reported after intra-arterial (brachial) injection of the medium. Also, brachial plexus injury has been reported with axillary artery injections.

During venography in the presence of venous stasis, inflammatory changes and thrombosis may occur. Thrombosis is rare if the vein is irrigated following the injection.

Diagnostic arteriograms may be obtained with 25 mL to 35 mL of HYPAQUE sodium 50 percent introduced into the larger peripheral arteries by percutaneous or operative methods. Visualization of veins in the extremities may be accomplished with 15 mL to 40 mL.

Pheochromocytoma. Administration of angiographic media to patients known or suspected to have pheochromocytoma can cause dangerous changes in blood pressure. A minimum dose should be injected. The blood pressure should be carefully monitored and measures for controlling major fluctuations should be available.

During aortography by the translumbar technique, extreme care is advised to avoid inadvertent intrathecal injection since the injection of even small amounts (5 mL to 7 mL) of the contrast medium may cause convulsions, permanent sequelae, or fatality. Should the accident occur, the patient should be placed upright to confine the hyperbaric solution to a low level, anesthesia may be required to control convulsions, and if there is evidence of a large dose having been administered, a careful cerebrospinal fluid exchange-washout should be considered.

The presence of a vigorous pulsatile flow should be established before using a catheter or pressure injection technique. A small "pilot" dose (about 2 mL) should be administered to locate the exact site of needle or catheter tip to help prevent injection of the main dose into a branch of the aorta or intramurally. In the translumbar technique, severe pain during injection may indicate intramural placement and abdominal or back pain afterwards may indicate hemorrhage from the injection site. ollowing catheter procedures, gentle pressure hemostasis for 5 to 10 minutes is advised, followed by observation for 30 to 60 minutes and immobilization of the limb for several hours to prevent hemorrhage from the site of arterial puncture.

The care and experience with which the procedure is performed, the amount and type of medium used, the age and condition of the patient, and the premedication and anesthesia employed, influence the incidence and severity of reactions or complications that may be encountered. Since aortography is not without some danger, it should be employed only by persons experienced in the technique.

Repeated injections of the solution during a single study should be avoided whenever possible.

Under conditions of slowed aortic circulation there is an increased likelihood of aortography causing muscle spasm. Occasional serious neurologic complications, including paraplegia, have also been reported in patients with aortic-iliac or even femoral artery bed obstruction, abdominal compression, hypotension, hypertension, spinal anesthesia, injection of vasopressors to increase contrast, and low injection sites (L2-3). In these patients the concentration, dose, and number of repeat injections of the medium should be maintained at a minimum with appropriate intervals between injections. The position of the patient and catheter tip should be carefully evaluated.

Aortic Branches. Since serious neurologic complications, including quadriplegia, have occasionally been reported following spinal arteriography or selective injection of arterial trunks providing spinal artery branches (usually the thyrocervical, costocervical, subclavian, vertebral, bronchial, intercostal), great care is necessary to avoid entry of a large concentrated bolus of the medium. Thus, a "pilot" dose may establish correct position of the catheter tip. The concentration of the medium should not be over 50 percent. The carefully individualized dose is usually under 5 mL but preferably 3 mL to 4 mL and the number of repeat injections held to a minimum with appropriate intervals between injections. Pain or muscle spasm during the injection may require reevaluation of the procedure.

The most common reaction to the medium is a mild burning sensation on injection. In addition to the reactions described in the general section, the following have been reported: mesenteric and intestinal necrosis, acute pancreatitis, renal shutdown (usually transitory), and neurologic complications following inadvertent injection of a large part of the aortic dose into a branch of the aorta. Entry of the large aortic dose into the renal artery can cause, even in the absence of symptoms, albuminuria, cylindruria, and hematuria, and an elevated BUN. Rapid and complete return of function usually follows. Also reported are coronary occlusion, hemorrhage from puncture site, arterial perforation by catheter or needle, thrombosis, embolism, and subintimal injection with aortic dissection by the medium.

The amount of each individual dose is a more important consideration than the total dosage used. Sufficient time should elapse between each injection to allow for subsidence of hemodynamic disturbances.

Retrograde (catheter) aortography—For adults and children, 0.5 mL to 1 mL per kg of bodyweight.

Intravenous aortography—For adults and children, 1 mL per kg of body weight.

Translumbar aortography—For adults, 10 mL to 30 mL. For children under 12 years, the dose is proportionate to age.

Selective renal arteriography—For adults and children over 14 years of age, 5 mL to 8 mL with repeat injections as indicated. For younger children, the dose is proportionate to age.

After aspiration of 4 mL of marrow, 10 mL to 20 mL of the medium are injected.

To visualize the pterygoid venous plexus, 5 mL to 8 mL of the contrast medium are injected into the medullary cavity of the mandible.

In the presence of acute pancreatitis, direct cholangiography, if necessary, should be employed with caution, injecting no more than 5 mL to 10 mL without undue pressure.

Adverse reactions may often be attributed to injection pressure or excessive volume of the medium, resulting in overdistention. Such pressure may produce a sensation of epigastric fullness, followed by moderate pain in the back or right upper abdominal quadrant, which will subside when injection is stopped.

Hepatobiliary reflux of the medium may cause a pancholangitis or hepatitis which is usually transitory. Retrograde spread of the infection may produce liver abscess or septicemia. Pancreatic duct reflux may cause a transitory increase in serum amylase for a period of 6 to 18 hours without ill effects. Rarely it may cause pancreatitis.

The solution should be warmed to body temperature before administration. The injection is made slowly without undue pressure, taking great care to avoid introducing bubbles.

Operative—If no resistance is encountered, from 10 mL to 15 mL of a 25 percent to 50 percent solution is injected or instilled into the cystic duct or common bile duct, as indicated. In patients with obstructive jaundice, 40 mL to 50 mL of the medium may be injected directly into the gallbladder after aspiration of its contents.

Postexploratory or completion T tube cholangiography may also be performed after exploration of the common bile duct.

Postoperative—Delayed cholangiograms are usually made from the fifth to the tenth postoperative day prior to removal of the T tube.

In case of a dilated ductal tract, a larger volume (up to 100 mL) of radiopaque medium may be required for complete filling and visualization.

Percutaneous transhepatic cholangiography is contraindicated in patients with coagulation defects and prolonged prothrombin times until normal, or near normal, coagulation is achieved, eg, with vitamin K.

Percutaneous transhepatic cholangiography should only be attempted when compatible blood for potential transfusions is in readiness and emergency surgical measures are available. The patient should be carefully monitored for at least 24 hours to insure prompt detection of bile leakage and hemorrhage. Cholespastic premedication, as with morphine, should be avoided. Respiratory movements should be controlled during introduction of the needle.

In percutaneous transhepatic cholangiography, some discomfort is common, but severe pain is nusual. Complications of the procedure are often serious and have been reported in four to six percent of patients. These reactions have included bile leakage and peritonitis, which are more likely to occur in patients with obstructions that cause unrelieved high biliary pressure. Bleeding (sometimes massive with exsanguination) may occur, especially in patients with clotting abnormalities. Blood-bile fistula, manifested by an early urogram (within 2 minutes), has been reported. Hypotension with fever and chills, as manifestations of septicemia, have occurred. Tension pneumothorax, cholangitis, and bacteremia have been reported.

As the needle is advanced or withdrawn, a bile duct may be located by frequent aspiration for bile or mucus into syringe filled with normal saline. As much bile as possible is aspirated. The usual dose of HYPAQUE sodium 50 percent is 20 mL to 40 mL but the range can be from 10 mL to 60 mL depending on degree of biliary dilatation present. The injection may be repeated for exposures in different planes. If a duct is not readily located by aspiration, entry may be established by injection of successive small doses of 1 mL to 2 mL of the medium under x-ray observation as the needle is withdrawn. If a duct is not located after three or four attempts, the procedure should be abandoned. Inability to enter a duct strongly suggests hepatocellular disease.

The procedure should not be performed during the menstrual period or when menstrual flow is imminent, nor should it be performed when infection is present in any portion of the genital tract, including the external genitalia. The procedure is also contraindicated for pregnant women or for those in whom pregnancy is suspected. Its use is not advised for six months after termination of pregnancy, or 30 days after conization or curettage.

In patients with carcinoma or in those in whom the condition is suspected, caution should be exercised to avoid possible spread of the lesion by the procedure.

Cramping may occur during the injection and sometimes mild lower abdominal pain may be present for an hour or two afterwards. Even when the medium gains entrance into venous or lymphatic channels, systemic effects are rare. Generalized urticaria or slight transient hyperpyrexia, however, has been reported.

Splenoportography is usually performed under mild preoperative sedation and under local anesthesia.

Splenoportography should not be performed on any patient for whom splenectomy is contraindicated, since complications of the procedure at times make splenectomy necessary. Other contraindications include prolonged prothrombin time or other coagulation defects, significant thrombocytopenia, and any condition which may increase the possibility of rupture of the spleen.

Prior gastrointestinal x-ray examination should include particular attention to the lower esophageal area. A hematologic survey, including prothrombin time and platelet count, should be performed. To minimize risk of bleeding, manipulation during or after entry of the needle should be avoided. Caution is advised in patients whose spleen has recently become tender and palpable.

Following splenoportography, the patient should lie on his left side for several hours and should be closely observed for 24 hours for signs of internal bleeding.

Internal bleeding is the most common serious complication of splenoportography. Although leakage of up to 300 mL of blood is apparently not uncommon, sometimes blood transfusions and rarely, splenectomy, may be required to control hemorrhage. Peritoneal extravasation may cause transient diaphragmatic irritation or mild to moderate transient pain which may sometimes be referred to the shoulder, the periumbilical region, or other areas. Because of the proximity of the pleural cavity, accidental pneumothorax has been known to occur. Inadvertent injection of the medium into other nearby structures is not likely to cause untoward consequences.

A preliminary small "pilot" dose is injected to confirm splenic entry, followed usually by rapid injection of 20 mL to 25 mL of HYPAQUE sodium 50 percent. Rapid serial exposures are started with the injection of the dose and continued until contrast is observed in the entire portal system.

Metastatic Brain Lesions: Large doses of contrast media should be avoided in patients with suspected metastatic brain lesions. Intravenous administration of large doses to these patients is more likely to result in convulsions; however, these occurrences are rare. This has been attributed to tissue accumulation of the medium in the presence of blood brain barrier disruption caused by disease. Appropriate measures for seizure management should be immediately available.

Convulsion: (See PRECAUTIONS—General).

Bolus intravenous injection of 50 mL to 100 mL, or up to 150 mL by infusion. The rate of injection and the timing of scans will depend principally on the expected nature of the pathology. Dosage in children is proportional to adults, based on weight.