Radiographic Contrast


Radiographic Examination Requiring Contrast

  • General Comments
    • Approximately 10 Million Diagnostic Examinations Using Radiographic Contrast are Performed Each Year in the US
  • Angiogram
  • Arthrogram
  • Computed Tomogram (CT)
  • Endoscopic Retrograde Cholangiopancreatography (ERCP) (see Endoscopic Retrograde Cholangiopancreatography, [[Endoscopic Retrograde Cholangiopancreatography]])
  • Myelogram
  • Retrograde Urogram
    • Retrograde Pyelogram
  • Urogram
    • Pyelogram
  • Venogram

Radiographic Contrast Agents (Selected)

  • Omnipaque 350 (Iohexol 75.5%): non-ionic monomer
    • Osmolality: 844 mosm/kg
    • Iodine: 350 mg/mL
  • Visipaque 270 (Iodixanol): non-ionic dimer
    • Osmolality: 290 mosm/kg
    • Iodine: 270 mg/mL


Radiographic Contrast Agents are Benzoic Acid Molecules with Three Atoms of Iodine Replacing the Hydrogen Atoms on the Benzene Ring

  • Distinguishing Features of Contrast Agents
    • Charge of Iodinated Molecule (Ionic vs Non-Ionic)
    • Molecular Structure (Monomeric vs Dimeric)
    • Osmolality of Formulation
      • Hyperosmolal: >1400 mosm/kg
      • Hypo-Osmolal: 500-900 most/kg
      • Iso-Osmolal (Isotonic Relative to Serum): 290 mosm/kg

Adverse Effects

General Comments

  • Most Adverse Reactions are Associated with Intravenous Radiographic Contrast Administration
    • However, Adverse Reactions May Also Occur with Intra-Arterial Administration, Non-Vascular Administration (Retrograde Pyelogram, etc)

Chemotoxic Reaction (“Physiologic Reaction”)

  • Epidemiology
    • Relationship to Dose/Infusion Rate: chemotaxic reactions are dose-dependent and infusion rate-dependent
  • Physiology
    • Chemotoxic Reactions are Related to the Chemical Properties of the Specific Contrast Agent
  • Clinical: usually transient and self-limited
    • Arm Pain: associated with both intravenous or intra-arterial infusions
    • Flushing (see Flushing, [[Flushing]])
    • Seizures (see Seizures, [[Seizures]])
    • Nausea/Vomiting (see Nausea and Vomiting, [[Nausea and Vomiting]])
    • Warmth
  • Management
    • Chemotoxic Reactions Do Not Preclude Further Use of the Contrast: slowing the infusion rate may be sufficient

Vasovagal Reaction (see Vasovagal Episode, [[Vasovagal Episode]])

  • Epidemiology: common
    • Relationship to Dose/Infusion Rate: vasovagal reactions are dose-dependent and infusion rate-dependent
  • Physiology
    • Depressed Sinoatrial and Atrioventricular Nodal Activity
    • Increased Vagal Tone
    • Inhibition of Atrioventricular Nodal Conduction
  • Clinical
  • Management
    • Vasovagal Reactions Do Not Preclude Further Use of the Contrast: slowing the infusion rate may be sufficient
    • Atropine (see Atropine, [[Atropine]]): may be required for symptomatic bradycardia

Immediate Hypersensitivity Reaction

  • Epidemiology
    • Age: most commonly seen in patients 20-50 y/o
      • Immediate hypersensitivity reactions are uncommon in children
    • Relationship to Osmolality: the osmolality of the contrast is the characteristic most strongly associated with the risk of immediate hypersensitivity reaction
      • Mild-Moderate Immediate Hypersensitivity Reaction: occurs in 5-13% of ionic high osmolality agents, but only in 0.2-3% of non-ionic low osmolality agent
    • Relationship to First Exposure: approximately 33% of immediate hypersensitivity reactions occur on first exposure to the contrast agent
    • Idiosyncratic and Independent of Dose/Infusion Rate: immediate hypersensitivity reactions may occur with even small amounts of contrast [MEDLINE]
    • Onset: develop within 1 hr after contrast administration (usually within 5 min)
    • Relationship to Seafood/Shellfish Allergy: seafood/shellfish allergy is not an independent risk for factor contrast-induced immediate hypersensitivity (this is a common misperception)
  • Risk Factors for Immediate Hypersensitivity Reaction
    • Allergic Disease
      • Allergic Rhinitis (see Allergic Rhinitis, [[Allergic Rhinitis]]): atopy clearly increases the risk of immediate hypersensitivity reaction to contrast
      • Asthma (see Asthma, [[Asthma]]): inconsistent risk factor in studies
      • Atopic Dermatitis (Eczema) (see Atopic Dermatitis, [[Atopic Dermatitis]]): atopy clearly increases the risk of immediate hypersensitivity reaction to contrast
      • Food Allergy (see Food Allergy, [[Food Allergy]]): atopy clearly increases the risk of immediate hypersensitivity reaction to contrast
    • Prior Immediate Hypersensitivity Reaction to Radiographic Contrast
      • Repeated Exposure to Radiographic Contrast Increases the Risk of Both an Immediate Hypersensitivity Reaction and a Severe Immediate Hypersensitivity Reaction
    • Medications: these are controversial risk factors
  • Physiology
    • IgE-Mediated: some cases
      • Contrast-specific IgE antibodies have been demonstrated in several studies (Am J Roentgenol, 2008) [MEDLINE] (Allerg Immunol, 1993; Paris) [MEDLINE]
    • Non-IgE-Mediated: most cases
      • Activation of Coagulation/Kinin/Complement Cascades
      • Direct Mast Cell Activation
      • Inhibition of Cholinesterase
      • Inhibition of Platelet Aggregation with Increased Serotonin Release
  • Diagnosis
    • Serum Tryptase: may be detectable for several hours after immediate hypersensitivity reaction (although elevations are best detected between 30 min-3 hrs after the event)
      • Half-Life of Serum Tryptase: 90 min
      • However, a normal serum tryptase level does not exclude the diagnosis of anaphylaxis
  • Clinical
    • Anaphylaxis (see Anaphylaxis, [[Anaphylaxis]])
    • Angioedema (see Angioedema, [[Angioedema]])
    • Bronchospasm/Wheezing (see Obstructive Lung Disease, [[Obstructive Lung Disease]])
    • Coronary Artery Vasospasm: associated with coronary angiography
    • Flushing (see Flushing, [[Flushing]])
    • Hypotension (see Hypotension, [[Hypotension]])
    • Laryngeal Edema/Stridor (see Stridor, [[Stridor]])
    • Laryngospasm (see Laryngospasm, [[Laryngospasm]]): hoarseness may occur
    • Loss of Consciousness
    • Pruritus (see Pruritus, [[Pruritus]])
    • Sinus Tachycardia (see Sinus Tachycardia, [[Sinus Tachycardia]]): usually assists in differentiation from vasovagal episode (where bradycardia is more commonly observed)
    • Urticaria (see Urticaria, [[Urticaria]])
  • Prevention
    • Use of Low Osmolality Contrast for All Intravascular Procedures: common practice in most settings
    • Use of Non-Ionic Low Osmolality Contrast in Patients with Prior Serious Allergic Reaction to Materials Other Than Radiographic Contrast, Patients Receiving Contrast by Power Injector, and Possibility of Increased Risk for Immediate Hypersensitivity Contrast Reaction
    • Premedication for Patients without Prior Contrast Reaction
      • Provided that a non-ionic low osmolality agent is used, administration of premedication in patients without prior contrast reaction is not supported by the evidence
      • Extravascular procedures (cystogram, etc) do not require premedication, due to lower risk of immediate hypersensitivity reaction
    • Premedication for Patients with Prior Contrast Reaction: indicated
      • Diphenhydramine (Benadryl) (see Diphenhydramine, [[Diphenhydramine]]): administer 1 hr (PO or IV) before procedure
      • Methylprednisolone (Solumedrol) (see Methylprednisolone, [[Methylprednisolone]]): may be used instead of prednisone at same time intervals
      • Prednisone (see Prednisone, [[Prednisone]]): administer 50 mg 13 hrs, 50 mg 7hrs, and 50 mg 1hr prior to procedure
  • Treatment
    • Discontinue Contrast Administration: do not restart contrast if immediate hypersensitivity reaction is suspected (even if symptoms rapidly resolve)
    • Treatment of Anaphylaxis (see Anaphylaxis, [[Anaphylaxis]]): standard treatment
    • Corticosteroids (see Corticosteroids, [[Corticosteroids]]): although commonly used, they do impact acute symptoms, but may be beneficial in preventing/decreasing severity of the delayed symptoms (although data is lacking)
  • Prognosis
    • Mortality Rate: age-related -> higher mortality rates in older patients

Delayed Hypersensitivity Reaction

  • Epidemiology
    • Onset: develop within 1 hr-several days after contrast administration
  • Physiology: delayed hypersensitivity reactions are idiosyncratic and independent of dose and infusion rate [MEDLINE]
    • May Occur with Even Small Amounts of Contrast
  • Clinical

Endocrinologic Adverse Effects

Hypothyroidism (see Hypothyroidism, [[Hypothyroidism]])

  • Physiology: due to iodine content

Gastrointestinal Adverse Effects

Acute Pancreatitis (see Acute Pancreatitis, [[Acute Pancreatitis]])

  • Epidemiology: endoscopic retrograde cholangiopancreatography (ERCP) contrast has a probable association with pancreatitis

Neurologic Adverse Effects

Posterior Reversible Encephalopathy Syndrome (PRES) (see Posterior Reversible Encephalopathy Syndrome, [[Posterior Reversible Encephalopathy Syndrome]])

  • Epidemiology: xxx
  • Physiology: xxx

Pulmonary Adverse Effects

Radiographic Contrast-Induced Leukostasis with Acute Respiratory Distress Syndrome (ARDS) (see Leukostasis, [[Leukostasis]] and Acute Respiratory Distress Syndrome, [[Acute Respiratory Distress Syndrome]])

  • Epidemiology: reported with diatrizoate
  • Physiology: complement activation with generation of C5a -> granulocyte aggregation and adherence to endothelium -> granulocytes obstruct pulmonary capillaries and arterioles and release proteases and oxygen radicals -> endothelial damage and capillary leak syndrome
    • Increased plasma histamine levels
  • Clinical: dyspnea and hypoxemia begin within minutes-1 hr of contrast injection
  • Treatment: corticosteroids may be effective (see Corticosteroids, [[Corticosteroids]])

Diffuse Alveolar Hemorrhage (DAH) (see Diffuse Alveolar Hemorrhage, [[Diffuse Alveolar Hemorrhage]])

  • Epidemiology: xxx
  • Physiology: absence of pulmonary capillaritis (bland alveolar hemorrhage)

Renal Adverse Effects

Contrast Nephropathy (see Contrast Nephropathy, [[Contrast Nephropathy]])

  • Epidemiology
  • Clinical
  • Treatment


  • Fatal complement-induced leukostasis after diatrizoate injection. Principles of clinicopathologic diagnosis. JAMA. 1983 Nov 4;250(17):2340-2 [MEDLINE]
  • Ionic versus nonionic contrast media: a prospective study of the effect of rapid bolus injection on nausea and anaphylactoid reactions. J Comput Assist Tomogr. 1998;22(3):341 [MEDLINE]