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Currently there is no contrast medium on the market that is considered to be ideal, but the ideal contrast medium should fulfill certain requirements for safe and effective application. It should be:
Easy to administer
A stable compound
Concentrated in the required area when injected
Rapidly eliminated when necessary
Of appropriate viscosity for administration
Tolerated by the patient
Contrast media are can divided into two main categories. There are negative contrast media and positive contrast media. The first negative contrast media which are radiolucent and of low atomic number, causing the part in which it is placed to be more readily penetrated by x-rays that the surrounding tissue; as they attenuate the x-ray beam less in effect than body tissue, they appear darker on the x-ray image. Gasses are commonly used to produce negative contrast on radiographic images. The second type is positive contrast media; these are radio opaque and are of a high atomic number, causing the part in which it is placed to be less readily penetrated by x-rays than the surrounding tissue. Consequently this contrast agent-filled area appears denser than body tissue.
Barium and iodine based solutions are used in medical imaging to produce positive contrast. Both positive and negative contrast can be employed together in double contrast examination to produce a radiographic image. Double contrast is used primarily in the alimentary tract but is also used in arthrography of joints. The positive contrast medium is used to coat the walls of the cavity and the negative contrast, in the form of a gas, is used to distend the area being imaged. Double contrast examinations permit optimum visualization by producing a high inherent contrast whilst allowing adequate penetration of the area under examination. Use of a small amount of contrast agent in conjunction with the distended cavity allows coating of the structures in the cavity (or in the case of the alimentary tract, the mucosal lining) which provides better detail of the area when the thin coating is shown in contrast to the gas-filled area, rather than using large amounts which may be dense enough to mask important information.
NEGATIVE CONTRAST MEDIA
Some of gases create negative radiographic contrast on images:
Air: introduced by the patient during a radiographic examination, e.g. inspiration during chest radiography or can also be introduced by the radiographer as part of the examination in a double contrast barium enema.
Oxygen: identified into cavities of the body for example to demonstrate the knee joint we have to do an arthrogram.
Carbon dioxide: recognized into the gastrointestinal tract in conjunction with a barium sulfate solution to show the mucosal pattern, e.g. double contrast barium meal. For the barium meal it is formulated as effervescent powder sulfate (e.g. 'carbon' granules) or ready mixed carbonated barium sulfate (e.g.'Baritop'). Carbon dioxide can also be introduced into the colon when performing a double contrast barium enema. It has been recommended that carbon dioxide be used as the negative contrast agent in a double contrast barium enema, rather than air, as it cause delay abdominal pain as well as less post procedural pain and discomfort. However, some studies have shown that carbon dioxide can also be used as an alternative contrast to iodinated contrast for diagnostic angiography and vascular interventions in both the arterial and venous circulation. The gas produces negative contrast due to its low atomic number and low density compared with adjacent tissues.
POSITIVE CONTRAST MEDIA
Barium and iodine solutions are used to create positive contrast on images.
Barium sulfate solutions (BaSO4) used in gastrointestinal imaging
Barium solutions are connected with contrast media used for radiographic examinations of the gastrointestinal tract. The next characteristics of barium solutions make them convenient for imaging of the gastrointestinal tract:
High atomic number (56) producing good radiographic contrast
Impossible to dissolve
Relatively not expensive
Excellent coating properties of the gastrointestinal mucosa
Barium suspensions are composed from pure barium sulfate mixed with additives and dispersing agents, held in suspension in water. Compounds to become stable the suspension are added; these act on the surface tension and increase solution viscosity. A dispersing agent to prevent sedimentation is added, ensuring an even distribution of particles within the suspension. Also added to the suspension is a deforming agent, employed to prevent bubbles that may mimic pathology in the gastrointestinal tract. Flavorings are usually added to oral solutions, making them more palatable for patients.
The concentration of barium in the solution is normally stated as a percentage weight to volume ratio (w/v). A 100% w/v solution contains 1g of the barium sulfate per 100ml of water; the density of the barium solution is therefore dependent upon the weight volume. There are many varieties of barium suspensions available and the type used is dependent upon the area of the gastrointestinal tract being imaged. It also depends greatly upon the individual preferences of the practitioner.
Patients rarely have allergic reactions to barium sulfate solutions but may react to the preservatives or additives in the solutions. Barium sulfate preparations are usually safe as long the gastrointestinal tract is patient and intact. A severe inflammatory reaction may develop if it is extravagated outside the gastrointestinal tract; this is most likely to occur when there is a perforation of the tract. If barium sulfate escapes into the peritoneal cavity, inflammation and peritonitis may occur. Escaped barium in the peritoneum causes pain and hypovolaemic shock and, despite treatment which includes fluid replacement therapy, steroids and antibiotics, there is still a 50% mortality rate; of those who survive, 30% will develop peritoneal adhesions and granulomas.4 Aspiration of barium solutions during upper gastrointestinal tract imaging is considered to be relatively harmless. It most frequently affects the elderly patient. Physiotherapy is usually required in order to drain the aspirated barium and should be performed before the patient leaves the department.
Oral barium sulfate should not be administered in cases of obstruction as it may inspissations behind an obstruction, compounding the patient's problem. Sedated patient should not undergo examinations of the upper gastrointestinal tract as their swallowing reflex may be diminished.
When preparing the barium solutions for administration it is important to check expiry dates and ensure the packaging is intact. Solutions administered rectally should be administered at body temperature to improve patient tolerability and also reduce spasm of the colon. It is important that the administrator knows the patient's medical history and check for any contraindications prior to administration. Barium sulfate solutions are contraindicated for the following pathologies;
Suspected fistula or to check an anastomosis site
Suspected partial or complete stenosis
Hemorrhage in the gastrointestinal tract
Prior to surgery or endoscopy
If the patient has had a recent gastrointestinal wide bore biopsy (usually within 3-5 days)
When barium sulfate solutions are contraindicated for gastrointestinal imaging, water-soluble, iodine-based contrast medium (e.g. Gastrografin or Gastromiro) should be employed. These can be administered orally, rectally or mechanically, e.g. via stomas. The iodine concentration of Gastrografin= 370 mg/ml-1 and gastromiro=300 mg/ml-1. When used for imaging the gastrointestinal tract, water-soluble contrast produces a lower contrast image than barium due to its lower atomic number.
The patients consent must be given prior to the administration of barium contrast solutions. The patient should be reassured about examination and given the opportunity to ask questions. It is important when using barium sulfate solutions that associated pharmacological agents such as buscopan and glucagon are fully understood and the indications and contraindications adhered to ensuring their safe application.
Iodine-based contrast media used in medical imaging
The largest group of contrast media used in imaging departments is the water-soluble organic preparations in which molecules of iodine are the opaque agent. These compounds contain iodine atoms (iodine has an atomic number of 53), bound to carrier molecule. This holds the iodine in a stable compound and carries it to the organ under examination. The carrier molecules are organic, containing carbon, and are of low toxicity and high stability. Iodine is used as it is relatively safe and the k-shell electron) and is therefore close to the mean energy of diagnostic x-rays. The selection of kVp used for imaging examinations utilizing iodine-based contrast plays a part in providing optimal attenuation. The absorption edge of iodine (35keV) predicts that 63-77 kVp is the optimal range. The iodine-based compounds are divided into four groups depending upon their molecular structure; the four groups are:
POSSIBLE SIDE-EFFECTS OF IONIC-BASED CONTRAST MEDIA
Any water-soluble ionic contrast introduce into the vascular system can cause potential physiological adverse effects. These effects are caused by the high osmolarity and chemo toxic effects of the median. Although both ionic and non-ionic iodine media have physiological effects on the body, ionic media are of higher osmolarity and potentially cause more side-effects in the patient. An ionic contrast has approximately five times the osmolarity of human plasma (I.e. it is hyperosmolar). Water-soluble organic iodine contrast media have two effects: the desirable primary effect of attenuating x-rays and providing the radiographic image with adequate contrast and the unwanted secondary effect of inducing potential side-effects in patients.
Primary effect - image contrast
Optimum attenuation is achieved by selecting the appropriate concentration of iodine in solution for the examination undertaken. Two solutions with the same iodine content should provide the same iodine concentration in blood after intravenous injection. This is not the case and the concentration may be affected by small molecules diffusing out of the blood vessel lumen, or by solutions of high concentration within the blood vessel drawing water out of adjacent cells by osmosis (therefore diluting the solution), as mentioned in the introduction to this chapter. To illustrate this, remembering that osmolatity is defined as the number of solute particles (e.g. the contrast media molecules) dissolved in 1L (1000g) of water, a comparison between normal blood plasma osmolality and different contrast agents is shown:
Normal blood plasma - 300 mOsm/kg water
Ionic monomer - 1200-2400 mOsm/kg water, making it very hypertonic
Ionic dimmers, and non-ionic monomers and dimmers (LOCM) are still hypertonic but to a much lesser degree, reducing the osmotic activity, however they are more expensive. Isotonic iodixanol (visipaque) has approximately a third the osmolality of the non-ionic media and a sixth that of the monomeric ionic media of equip-iodine concentration (i.e. 290 mOsm/kg water vs 844 and 1800 mOsm/kg water respectively)
When comparing two contrast media of the same iodine concentration, a higher venous concentration of iodine is obtained when diffusion of contrast medium is slowed down by using large molecules (dimers) and osmotic affects are decreased by decreasing the number of molecules/ions in solution (monomers).
Secondary effect - adverse events
Contrast media are specifically designed to minimize secondary effect or adverse reaction. The 'perfect' contrast agent would cause no adverse affects at all. Acute adverse reactions do occur, however, and are defined as reactions that occur within 1hour after administration of the contrast medium. Adverse reactions to contrast media or drugs are generally classified into two categories:
Idiosyncratic reactions which are dose dependent and unpredictable, having a prevalence of 1-2% (0.04-0.22% severe) and are fatal in 1 in 170000.
Non-idiosyncratic reactions are dividing into chemotoxic and osmotoxic reactions. They are predictable and more likely to occur in debilitated patients or patients in poor medical health. They are dose dependent and are caused primarily by osmotic effects causing shifts in fluids from the intracellular structures, causing cell dehydration and dysfunction.
The onset of reactions is variable; 70% of reactions occur within 5minutes after injection, 16% occur more than 5minutes after injection and remaining 14% within 15minutes of the injection. It is advisable that a suitably qualified staff member remains with the patient for at least 15minutes post injection. Contrast media affect specific organs or systems of the body; the following are a summary of some of the major systemic effects of contrast media.
What happens during a reaction and how reactions may be prevented
Improvements in the chemical structure of contrast medium molecules have resulted in a significant reduction in the number of acute reactions. Severe reactions are a rare occurrence and previous allergic reactions to contrast material, asthma, and known allergies are factors associated with in increased risk of developing a reaction. An injection of contrast medium causes the release of histamine from the basophiles and mast cells in the blood. Some patients release more histamine than others and the reason for this is still not fully understood. Another possible mechanism for reactions to contrast media is thought to be the inhibition of enzymes, e.g. cholinesterase, which deactivates and hydrolyses acetylcholine, causing symptoms of vagal overstimulation resulting in bronchospasm and cardiovascular collapse.
Patients must be assessed and past medical history ascertained before any contrast medium is administered. Any patients with a medical history that raises concern can be given prophylactic treatment before administered of contrast material, to prevent potential reactions. Injection of hydrocortisone may be given before the contrast agent to suppress inflammatory and allergic reactions, including anaphylaxis renal failure or a possible life-threatening emergency. Prophylactic drugs should be administered in a separate syringe as they may cause crystallization when they come into contact with contrast media. Serious reactions still occur, and awareness and treatment of the different types of reaction is paramount for any staff member involved in intravenous administered of contrast media.
Figure Contrast media images.