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Chapter: Modern Medical Toxicology: Miscellaneous Drugs and Poisons: Gastrointestinal and Endocrinal Drugs

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Radiocontrast Agents

Most radiocontrast agents in use are iodinated contrast material which may be ionic or non-ionic compounds.

RADIOCONTRAST AGENTS

Most radiocontrast agents in use are iodinated contrast material which may be ionic or non-ionic compounds.

Classification

·              Higher-osmolality contrast agents (HOCA)—These are mostly ionic compounds and have been in use for several decades. They are relatively cheap and safe, though occasionally severe adverse reactions can occur.

·              Lower-osmolality contrast agents (LOCA)—These are mostly non-ionic compounds which cause less discomfort and are associated with a lower incidence of severe adverse reac-tions. However they are quite expensive.

Uses

·      Urography: The agents used for urography comprise mainly small molecule, water soluble, low protein binding, high plasma concentration compounds which are given IV.

Examples—

o     Ionic monomers: diatrizoates, iothalamates, metrizoates, iodamide, ioxithalamate.

–  Ionic dimers : ioxaglic acid.

– Non-ionic monomers : iohexol, iopamidol, ipro-mide, iopentol, metrizamole.

–  Non-ionic dimers : iotralan, iodixanol. Angiography: These agents are water soluble, with low viscocity and radiodensity.

·              Examples:

–  Non-ionic monomers: iohexol.

Contrast radiography of GI tract: These are nonabsorbable agents which form a homogenous coat on the GI mucosa and do not interact with GI secretions.

·              Examples:

––  Barium sulfate.

Computerised tomography of GI tract: These are non-absorbable iodinated water-soluble agents with high osmo-lality.

·              Examples:

––  Diatrizoate. Myelography: Agents for this are non-ionic, water soluble, and miscible with CSF.

·              Examples:

––  Metrizamide, iotralan.

Lymphography, lymphangiography: These agents are water-insoluble with high radiodensity.

·              Examples:

––  Iodised oil, iotasol.

Magnetic resonance imaging: YYExamples:

–– Gadolinium, manganese, and iron as the aminopo-lycarboxylate chelates and gadopentetic acid.

Cholecystography, cholangiography: These agents are preferentially excreted in the bile after absorption from GI tract.

·              Examples:

–– Ipodates, iocetamic acid, iopanoic acid, sodium tyropanoate.

Adverse Effects

Contrast media are known for producing severe reactions, though they are relatively infrequent (1 or 2 per 1000 exami-nations) . Mild to moderate reactions are more common, but subside on their own.

■■Anaphylactoid reaction:

o     Predisposing factors:

–– Cerebral or renal disease in patient over the age of 50 years.

–– History of allergy (including asthma). –– History of cardiac disease.

––  History of reaction to contrast material.

–– Multiple myeloma, homocystinuria, sickle cell anaemia, phaeochromocytoma.

–– Previous study in which large dose of contrast material was used.

o     Categories of reaction:

–– Mild: nausea, vomiting, cough, headache, vertigo, itching, pallor, flushing, chills, sweats, rash (hives), nasal stuffiness, and swelling of face and eyes.

–– Moderate: moderate intensity of any of the above manifestations, with/without the following—pulse changes, hypo- or hypertension, dyspnoea, bron-chospasm, and laryngospasm.

–– Severe: life-threatening manifestations including severe laryngospasm, convulsions, arrhythmias, unresponsiveness and cardiopulmonary arrest.

Cardiovascular side effects:

o     Cardiac ischaemia with pain and arrhythmias, usually accompanied by dyspnoea. Hypotension with tachy- cardia is commonly observed.

o     ECG changes include sinus bradycardia, heart block, Q-T prolongation, ventricular tachycardia/fibrillation, and ST segment and T wave changes.

·              Gastrointestinal side effects: vomiting, abdominal pain.

·              Neurological side effects: Headache (may be associated with intracerebral haemorrhage), amnesia, visual blurring, cortical blindness, encephalopathy, vertigo, and convulsions.

·              Pulmonary side effects: Non-cardiogenic pulmonary oedema is relatively commonly reported.

·              Renal side effects: There have been several reports of acute renal failure following injection of water soluble contrast media. Table 32.9 lists important predisposing factors.



·              Clinically, there is acute tubular necrosis, presenting with oliguria within 24 hours of exposure to the agent.

A formula has been suggested for calculating the maximum dose of contrast material that can be given safely without compromising renal function:

Contrast agent (maximum limit)

·     Thromboembolic phenomena: Serious thromboembolic events causing myocardial infarction and stroke have occurred during angiographic procedures with contrast media. Careful intravascular administration is necessary to minimise such complications. The following is a list of precautions:

o     Continuous flushing with saline solution to prevent mixing of blood and contrast media, premedication with heparin, and use of plastic syringes are important safety measures when using non-ionic contrast media.

o     Non-ionic contrast media should not be mixed with blood before intravascular injection.

o     Extra caution should be exercised when using non-ionic contrast media in high-risk patients (elderly patients, patients with coagulation defects, etc.).

·              Thyroid complications: Since radiocontrast agents invar- iably contain iodides which cannot be metabolised by deiodinating enzymes, thyrotoxicosis may be induced in susceptible patients. Prophylactic treatment with sodium perchlorate 1.2 grams administered 30 minutes before, and 6 to 8 hours after exposure, has been suggested.

·              Cancer induction: Thorotrast, a contrast agent which contains 25% colloidal thorium dioxide has been associated with malignancies.

·              Precipitation of mumps: Iodide mumps has occasionally been observed in patients who were administered iodinated contrast agents.

Clinical (Toxic) Features

·      Inadvertent administration of ionic contrast agents such as diatrizoate or iodamine, instead of iopanidol, by the intrath-ecal route, has resulted in fatalities.

·      In the past, methiodal sodium was commonly used for myelography. Because of high incidence of neurotoxic adverse reactions, other compounds were subsequently introduced, e.g. iothalamate meglumine and iocarmate.

·      Inadvertent myelography with diatrizoate has led to lumbar pain, tonic-clonic convulsions, hyperthermia, rhabdomy-olysis, disseminated intravascular coagulation, renal failure, pulmonary oedema and death.

·      Overdose with iopanoic acid has led to vomiting, diarrhoea, hypotension, coronary insufficiency, acute hepatic necrosis, renal failure and death.

·      Overdose with iothalamate meglumine during excretory urography can lead to cardiopulmonary failure.

Treatment

Adverse Effects

·      Anaphylactoid reaction:

For urticaria:

––  Mild:

-- Diphenhydramine (50 mg oral/IM/IV), or hydroxyzine (25–50 mg oral/IM/IV).

--Cimetidine (300 mg oral/slow IV in 10 ml D5W soln), or ranitidine (50 mg oral/slow IV in 10 ml D5W solution).

––  Severe:

--  Adrenaline (1:1000) SC, 0.1 to 0.3 ml.

·              For facial/laryngeal oedema:

––  Mild:

-- Adrenaline (1:1000) SC, 0.1 to 0.3 ml; can be repeated up to 3 times (1 mg max).

-- Oxygen, 2 to 6 L/min. –– Severe:

--  Intubation.

·              For bronchospasm:

––  Oxygen, 2 to 6 L/min.

–– Adrenaline (1:1000) SC, 0.1 to 0.3 ml, or beta-agonist inhalers.

–– Aminophylline 6 mg/kg, IV, in D5W, slowly, or terbutaline 0.25 to 0.5 mg, IM/SC.

·              For hypotension with tachycardia:

––  Mild:

-- Trendelenburg position, oxygen, IV fluids (Ringer lactate > normal saline > D5W).

––  Severe:

-- Adrenaline (1:1000) SC, 0.1 to 0.3 ml ; repeat up to 3 times (1 gm max).

·              For hypotension with bradycardia:

–– Trendelenburg position, oxygen. –– Atropine 0.6 to 1 mg, slow IV.

––  IV fluids (Ringer lactate > normal saline > D5W).

·              For hypertension:

–– Apresoline 5 mg IV, or sodium nitroprusside. –– Monitor ECG, pulse oximeter, BP.

·              YY       For convulsions:

–– Oxygen, 2 to 6 L/min. –– Diazepam 5 mg, IV.

––  Phenytoin, 15–18 mg/kg, infusion at 50 mg/min.

·              For pulmonary oedema:

–– Head elevation, rotating tourniquets. –– Oxygen 2 to 6 L/min.

––  Furosemide 40 mg, slow IV.

––  Corticosteroids (optional).

Neurological side effects:

·              Convulsions must be treated with IV, diazepam,phenytoin, phenobarbitone, intubation, and intensive medical care.

·              If accidental intrathecal injection of ionic contrastmedia is suspected, the patient should not be permitted to lie down.

Pulmonary side effects:

·              Patients with a history of radiocontrast medium-related oedema should be given prophylactic corticosteroids.

Renal side effects:

·              All patients undergoing examination involving contrast media should be well hydrated, since dehydrationprecipitates renal dysfunction.

·              Acute renal failure has to be managed by dialysis.

Toxic Effects

1)  Accidental intrathecal administration of ionic contrast agents must be treated with appropriate circulatory support, intrathecal lavage, and anticonvulsant therapy.

2)  To decrease the incidence of side effects after myelography, the following have been suggested:

a)           Head elevation for 6 hours after the study.

b)          Avoidance of drugs that lower seizure threshold, e.g.

c)           phenothiazines, MAOIs, tricyclics, alcohol, etc.

3)  Overdose with iopanoic acid can be treated with IV fluids, alkalinisation of urine, and cholestyramine (said to be a chelator of iopanoic acid). Cardiac and respiratory moni-toring are mandatory.

4)  General recommendations:

a)           Patients with pre-existing renal impairment should be given 0.45% saline IV, for 12 hours before and 12 hours after administration of contrast agents.

b)          Low-osmolality contrast agents are preferable to high- osmolality agents.

c)           Pre-treatment with corticosteroids and antihistamines (with or without adrenaline), has been suggested to minimise reactions to contrast agents.

 

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