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Iohexol

A Review of its Pharmacological Properties and Use as a Contrast Medium in Myelography and Neuroangiography

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Summary

Iohexol is a water-soluble nonionic contrast medium, commonly used in diagnostic radiography of the brain and spinal cord. Although its diagnostic efficacy is similar to that of other iodinated contrast media, its tolerability profile is generally better than that of ionic and older nonionic media. Iohexol causes fewer neurotoxic events than ionic media and some nonionic agents (metrizamide) in patients undergoing myelography. Patient discomfort is, moreover, reduced after intravascular injection of iohexol compared with the ionic agents diatrizoate, metrizoate and iothalamate in neuroangiography. Iohexol has been used successfully in a small number of patients with previous anaphylactoid reactions without serious untoward effects.

In common with other newer nonionic agents, iohexol is generally more expensive than conventional ionic media. Nonionic agents are, however, routinely used in myelography and neuroangiographic investigations, where the risk of attendant adverse events is especially high; ionic agents are no longer used in myelography.

In conclusion, iohexol offers a similar diagnostic efficacy profile to that of other nonionic agents. Wider clinical experience is, however, required to determine whether tolerability differences exist between iohexol and other newer agents of this class. Nevertheless, iohexol should be considered a first-line contrast medium in neurological imaging procedures.

Pharmacodynamic Properties

Iohexol is a water-soluble, low osmolality, nonionic iodinated contrast medium, routinely used in neurological imaging procedures of the brain and spinal cord. Adverse responses seen after intrathecal or intravascular injections of iohexol are thought to be governed by its chemical and physical properties. Osmolality, for example, plays an important role.

Intrathecal injection. The development of nonionic contrast media (such as metrizamide and iohexol) brought about significant reductions in neurotoxicity compared with the older ionic agents, particularly after intrathecal use. Collective data from in vitro and in vivo animal studies suggest that iohexol is less likely to produce epileptogenic effects than ionic (diatrizoate, ioxaglate) and some nonionic agents (metrizamide and iopamidol). EEG abnormalities and detrimental changes in cognitive function and mood occurred less frequently in patients undergoing myelography with iohexol than with metrizamide. Iohexol produced no histological evidence of arachnoiditis in animals.

Intravascular injection. All iodinated contrast media produce some form of haemodynamic or rheological change when injected. Iohexol causes less vasodilation than high osmolality ionic media; this generally manifests as warmth, heat or pain. Although red blood cell deformation has not been reported in vitro, iohexol may cause erythrocyte aggregation. Leucocyte function may also be impaired. The anticoagulant effects of nonionic media are generally less pronounced than those of ionic agents. Nephrotoxicity is an important consideration in the elderly or in patients with underlying renal disease or diabetes mellitus undergoing neuroangiography.

Pharmacokinetic Properties

Iohexol is absorbed from CSF into the systemic circulation after intrathecal injection. Peak iodine blood concentrations occur immediately after rapid intravenous injection and within 2 to 6 hours after intrathecal administration.

Iohexol binds poorly to plasma proteins. Animal studies indicate that iohexol does not significantly cross the intact blood-brain barrier after intravascular administration. Some diffusion across the placental barrier probably occurs, although it is unclear to what extent iohexol is excreted in breast milk. Volume of distribution averages 0.56 L/kg after intrathecal administration and 0.17 L/kg after intravenous injection of iohexol.

Iohexol is not significantly metabolised, deiodinated or biotransformed. It is eliminated by renal excretion; approximately 90% of an injected dose is excreted in urine within the first 24 hours after administration. The terminal elimination half-life of iohexol ranges from approximately 2 to 8 hours after an intrathecal dose. Vascular compartment half-life is approximately 20 minutes.

Elimination of iohexol may be delayed in patients with renal impairment; extrarenal excretion (into bile) may occur in these individuals. Iohexol can be removed by haemodialysis.

Diagnostic Efficacy

Regardless of the procedure used (myelography or neuroangiography), iohexol produces excellent to good radiographic visualisation of the spinal cord/brain in >80% of patients. Similar findings have also been reported in a small number of children undergoing myelography. Nondiagnostic or suboptimal radiographs generally resulted from technical problems, underlying pathology or patient movement, rather than from the opacity of the contrast medium itself.

Comparative studies demonstrate that the diagnostic efficacy of iohexol is similar to that of other ionic (diatrizoate, iothalamate, ioxaglate and metrizoate) and nonionic (iodixanol, iopamidol, iopromide, iotrolan and metrizamide) agents. Because of their neurotoxic effects, ionic agents are no longer used in myelography; both types of contrast medium may, however, be used in selected patients undergoing neuroangiography.

Tolerability

Nonionic agents produce fewer complications than ionic agents.

Myelography. Headaches, mild to moderate pain (including backache), neckache and stiffness, and nausea and vomiting occur most frequently after intrathecal administration of iohexol. Symptoms generally occur within the first 24 hours after the procedure, are mild to moderate in severity and transient (usually disappearing within several days). Seizures have been reported rarely. The frequency and severity of adverse events appears to depend on several factors, including gender, age, radiographic technique, medical history and clinical findings. A similar profile of adverse events is seen in adults and children.

Comparative data suggest that iohexol is generally better tolerated than metrizamide. Findings from other studies comparing iohexol with iotrolan or iopamidol are, however, inconclusive.

Neuroangiography. Adverse events after intravascular administration of iohexol are usually mild to moderate, transient and occur within 24 hours of the procedure. Sensations of warmth are reported most frequently; other commonly described events include pain, visual disturbances, headaches and nausea. Cardiovascular and other CNS events (including paraesthesia, transient global amnesia and seizures) have also been documented in individual patients. Specific tolerability data in children undergoing neuroangiography are unavailable.

Iohexol has been used successfully without serious untoward effects in a small number of patients who had previously experienced anaphylactoid reactions. These individuals should be pretreated with antihistamines or corticosteroids.

Findings from comparative studies show that iohexol produces less patient discomfort (warmth) than diatrizoate, metrizoate and iothalamate. Results from studies investigating nonionic agents are, however, less conclusive.

Dosage and Administration

Iohexol is available in solutions of varying iodine concentrations: 140, 180, 210, 240, 300 and 350 mg/ml. The volume and concentration of iohexol used for a diagnostic procedure depend on the degree and extent of contrast required for the examination and on the equipment and technique used.

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    Malini Haria & Rex N. Brogden

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Various sections of the manuscript reviewed by: J.G. Bélanger, Department of Radiology, Ottawa Civic Hospital, Ottawa, Ontario, Canada; L-J. Dubé, Department of Medical Imaging, Hôpital Sainte-Justine, Montreal, Quebec, Canada; M.J. Eadie, Department of Medicine, University of Queensland, Royal Brisbane Hospital, Brisbane, Queensland, Australia; S. Halpin, Department of Neuroradiology, University Hospital of Wales, Cardiff, Wales; B. Kendall, Department of Radiology, Maida Vale Hospital, London, England; A.D. Korczyn, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; W.H. Matthai, Jr., Heart Institute of Southern New Jersey, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School at Camden, Camden, New Jersey, USA; I. Reider, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; T. Sand, Department of Neurology, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway; T. Tamura, Department of Orthopaedic Surgery, Josai Hospital, Yuki City, Ibaraki, Japan.

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Haria, M., Brogden, R.N. Iohexol. CNS Drugs 7, 229–255 (1997). https://doi.org/10.2165/00023210-199707030-00006

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