Tumors

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.

Nonneoplastic Conditions

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.

Blood Tests

Coagulation: Diatrizoate salts significantly inhibit all stages of coagulation. The fibrinogen concentration, Factors V, VII, and VIII are decreased. Prothrombin time and thromboplastin time are increased.

Platelet aggregation: High levels of plasma diatrizoates inhibit platelet aggregation.

Serum calcium: Diatrizoate salts may decrease serum calcium levels. However, this depletion of serum calcium may also be the result of the addition of chelating agents (edetate disodium) in the preparation of certain contrast media.

Red cell counts: Transitory decreases in red cell counts. Technetium-99m—RBC labeling interference.

Leukocyte counts: Decrease.

Urea nitrogen (BUN): Transitory increase (see CLINICAL PHARMACOLOGY).

Serum creatinine: Transitory increase.

Urine Test

Contrast media which are excreted in the urine, may interfere with some laboratory determinations eg, proteinuria, specific gravity, osmolality, or bacterial cultures.

Thyroid Function Test

Protein-bound iodine (PBI) and total serum organic iodine: Transient increase of both tests following urography have been noticed. The results of PBI and radioactive iodine uptake studies which depend on iodine estimations will not accurately reflect thyroid function for up to 16 days following administration of iodinated urographic media. However, thyroid function tests not depending on iodine estimations, eg, T3 resin uptake or free thyroxine assays are not affected.

Contraindication

Urography is contraindicated in patients with anuria.

Precautions

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.

Because of the possibility of temporary suppression of urine, it is wise to allow an interval of at least 48 hours before excretory urography is repeated in patients with unilateral or bilateral reduction of normal renal function. Inadvertent retrograde cystourethrography can cause malignant hyperthermia, disseminated intravascular coagulation and fatality.

Adverse Reactions

See ADVERSE REACTIONS—General.

Dosage and Administration

Precautions

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 60 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.

Angiography should be avoided whenever possible in patients with homocystinuria, because of the risk of inducing thrombosis and embolism.

Indication

HYPAQUE meglumine 60 percent may be administered for visualization of the cerebral vessels. In as much as cerebral angiography is a highly specialized procedure requiring the use of special techniques, it is recommended that HYPAQUE meglumine 60 percent be used for this purpose only by persons skilled and experienced in carrying out the procedure.

Contraindication

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.

Precautions

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.

Adverse Reactions

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 defect, 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. Inasmuch 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).

Dosage and Administration

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. Children require a smaller dose in proportion to weight. Light anesthesia may be required in these procedures.

Indications

HYPAQUE meglumine 60 percent may be administered for peripheral arteriography and for venography.

Precautions

See PRECAUTIONS—General. Extreme caution is advised in considering peripheral arteriography in patients suspected of having thromboangiitis obliterans (Buergers 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.

Adverse Reactions

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.

Dosage and Administration

Diagnostic arteriograms may be obtained with 20 mL to 40 mL of HYPAQUE meglumine 60 percent introduced into the larger peripheral arteries by percutaneous or operative methods. Visualization of veins in the extremities may be accomplished with 10 mL to 20 mL.

Contraindication

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).

Precautions

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.

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.

Adverse Reactions

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.

In percutaneous transhepatic cholangiography, some discomfort is common, but severe pain is unusual. 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.

Dosage and Administration

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 (sometimes up to 25 mL) of a 30 to 60 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 indirectly 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.

Percutaneous transhepatic cholangiography is recommended for carefully selected patients for the differential diagnosis of jaundice due to extrahepatic biliary obstruction or parenchymal disease. The procedure is only employed where oral or intravenous cholangiography and other procedures have failed to provide the necessary information. In obstructive cases, percutaneous transhepatic cholangiography is used to determine the cause and site of the obstruction to help plan surgery. The technique may also be of value in avoiding laparotomy in poor risk jaundice patients since failure to enter a duct suggests hepatocellular disease. Careful attention to technique is essential for the success and safety of the procedure. The procedure is usually performed under local anesthesia following analgesic premedication (eg, 100 mg meperidine intramuscularly).

As the needle is advanced or withdrawn, a bile duct may be located by frequent aspiration for bile or mucus into a syringe filled with normal saline. As much bile as possible is aspirated. The usual dose of HYPAQUE meglumine 60 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 the injection of successive small doses of 1 mL or 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.

Indication

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

Contraindications

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.

Precautions

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.

Adverse Reactions

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.

Dosage and Administration

A preliminary small "pilot" dose is injected to confirm splenic entry, followed usually by rapid injection of 20 mL to 25 mL of HYPAQUE meglumine 60 percent. Rapid serial exposures are started with the injection of the dose and continued until contrast is observed in the entire portal system.

Indications

Arthrography may be helpful in the diagnosis of posttraumatic or degenerative joint diseases, synovial rupture, the visualization of communicating bursae or cysts, and in meniscography. However, the technique is of little value unless the arthrograms are interpreted by well-trained personnel.

Contraindication

Arthrography is contraindicated when there is infection in or near the joint.

Precautions

See PRECAUTIONS—General. A strict, aseptic technique is required to avoid introducing infection.

Adverse Reactions

See ADVERSE REACTIONS—General. Injection of HYPAQUE meglumine 60 percent into the joint usually causes immediate but transient discomfort. However, delayed, severe, or persistent pain may occur occasionally. Severe pain often results from undue use of pressure or the injection of large volumes. Joint swelling after injection is rare. Effusion, occasionally requiring aspiration, can occur in patients with rheumatoid arthritis.

Dosage and Administration

The procedure is usually performed with analgesic premedication and under local anesthesia. The amount of HYPAQUE meglumine 60 percent injected depends solely on the capacity of the joint. The damaged joint may require doses greatly exceeding those for normal joints. As much fluid as possible should first be aspirated from the joint; then, the medium should be injected gently to avoid overdistention of the joint capsule. Passive manipulation is sometimes used to disperse the medium in the joint. Sometimes, a 1 mL or 2 mL test dose is injected; immediate pain may indicate extravasation or extracapsular injection which, if confirmed by x-ray, requires relocation of the needle.

A single injection is usually adequate for multiple exposures. Contrast is good during the first 10 minutes after injection, adequate at 10 to 15 minutes, and begins to fade at 15 to 25 minutes.

The following approximate volumes have been used in normal adult joints:

 

Knee, shoulder, hip—5 mL to 15 mL

 

Temporomandibular—0.5 mL

 

Other—1 mL to 4 mL

"Double contrast arthrography," using a mixture of the medium and air or a dilution of HYPAQUE meglumine 60 percent to a 30 percent concentration, has been employed.

Indications

Cervical discography is a more hazardous procedure than lumbar discography, and the interpretation of the cervical discograms is more difficult.

The injected medium gradually diffuses throughout the disc and is absorbed rapidly. In a normal disc, good contrast is evident for 10 to 15 minutes. In a ruptured disc, the medium is absorbed more rapidly. Aspiration of the medium on completion of discography is considered unnecessary.

Contraindication

Discography is contraindicated when there is infection or open injury near the region to be examined.

Warning

Inadvertent subarachnoid injection must be avoided since even the small dose of the medium used in discography might result in convulsions and death. The onset of signs of pain, cramps, or convulsions (requiring anesthesia) may occur within minutes to an hour.

Precautions

A strict, aseptic technique is required to avoid introducing infection. The examination should be postponed if local or systemic infection is present. In cervical discography, care should be taken to avoid contamination of the disc by inadvertent puncture of the esophagus. Laceration of the disc by use of a needle that has become barbed by forceful impingement on a vertebra, should be avoided. The patient should be cautioned not to move during introduction of the needle.

Adverse Reactions

In the normal disc, only minor discomfort will occur during injection. More discomfort will result if excessive pressure or volume is used. Pain is unusual and may indicate extravasation.

In the damaged disc, however, the injection can cause pain, sometimes severe, which mimics the symptoms. Transient backache or headache, as in lumbar puncture, often occurs. Extravasation from the disc into the lateral recesses and extradurally into the spinal canal or local soft tissue does not usually cause adverse effects.

During discography extreme care is advised to avoid inadvertent intrathecal injection since the injection of even small amounts 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.

Dosage and Administration

Discography is usually performed with parenteral analgesia or sedation, and under local anesthesia. To minimize disc and tissue trauma, a two-needle technique is usually employed. An 18 to 20 gauge needle is used to penetrate to the disc and then a very fine (25 or 26 gauge) lumbar puncture-type needle is inserted through the needle to penetrate the disc.

Because of the resistance encountered, it is difficult to inject more than 0.2 mL to 0.3 mL of HYPAQUE meglumine 60 percent into a normal disc. Occasionally, however, a cervical disc can accept up to 0.5 mL and a lumbar disc, 1 mL (rarely, 2 mL) before resistance is encountered. Mild discomfort with little or no frank pain may indicate a normal disc.

In ruptured and some abnormal discs, 1 mL to 2 mL or more can be introduced without resistance; and, particularly if only one disc has pathology, the patient usually experiences pain, sometimes severe, with distribution characteristic of his symptoms. To minimize the amount of HYPAQUE extravasated, no more than 2 mL is injected in any one disc.

The procedure should be planned so that the duration of the discogram allows multiple exposures with a single dose. It has been recommended for diagnostic reasons that the procedure (injection and discogram) be performed on one disc at a time. Injection of a number of discs under suspicion, however, may be performed as part of one procedure.

Precautions

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.)

Dosage and Administration

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.