Introduction

The development of contrast media and patient preparations is interlinked with the development of image quality. As early as 1901, the use of air as a contrast medium was being discussed and single contrast meals became accepted practice in 1905. By 1917, the development of a reasonably reliable technique for imaging the colon meant that radiological descriptions of pathologies, such as carcinoma, tuberculosis, diverticulosis, megacolon and polyps, had been made. By the 1920s, it was stated that ‘the examination of the stomach and intestinal canal has become one of the most important spheres of radiographic work’ (Knox, 1923). Poor image quality limited the visualization of the gastrointestinal (GI) tract to more advanced pathologies such as strictures. Therefore, positive contrast studies predominated. However, with the improvements made in the 1960s in the detail available radiographically and fluoroscopically, the value of double contrast techniques was quickly advocated and became standard practice. It was quickly recognized that visualization of the mucosal lining of the GI tract was possible when using a double contrast technique and that the removal of artefacts within the system was essential to accurate diagnosis. As a result, a range of preparations and contrast media (positive and negative) has been developed and refined to support the requirement for increasingly high quality imaging, and an expanding variety of modalities and techniques are now used to visualize the GI tract.

This chapter discusses the principles of patient preparation and the pharmacology of preparations, contrast media and other pharmaceutical products currently used in the imaging of the GI tract.

Preparation

The earlier a GI abnormality is detected, the more the aim of treatment can be preventative rather than curative, and curative rather than palliative (National Institute for Clinical Excellence, 2004; Centre for Reviews and Dissemination, 2004). Maximizing diagnostic sensitivity and specificity in GI imaging is therefore a high priority. Diagnostic imaging is comprised of a series of events which are only ever as good as the weakest part of the process, making patient preparation as important a factor as any other. Diagnostic accuracy can be compromised by the presence of artefacts, such as food in the stomach or feces in the large bowel. These can mask or mimic pathology. It is therefore important that such artefacts are removed before an examination is carried out (Hendry et al., 2007; Pickhardt, 2007).

There are a number of important considerations when adopting a preparation regime. The process of clearance must leave the colon clean but not have any macro- or microscopic effects on the mucosa or compromise the patient’s physiology (Holte et al., 2004). For example, the action of a bowel preparation on the mucosal lining of the bowel can affect the adherence of the barium solution used (Cittadini et al., 1999a, 1999b). The need to review the contrast used should be taken into account when a regime is adopted or amended. Efficacy of the preparation needs to be balanced with patient compliance and acceptability in respect of taste, volume and action (Chan et al., 1997; Brown and DiPalma, 2004; Hendry et al., 2007). While it may be desirable to have a single regime for all patients from an administrative point of view, patients vary in their physical ability and comorbidities which need to be considered along with the adverse effects and contraindications of the agents used (Beloosesky et al., 2003; Sweetman, 2007; British Medical Association and the Royal Pharmaceutical Society of Great Britain, 2008). Finally, the financial cost of laxatives available varies considerably and poor preparation has been shown to have increased consequential costs (Bartram, 1994; Rex et al., 2002).

Getting the preparation regime right is important from the patient, clinician and service provider perspectives, as can be seen in Box 3.1. An appropriate bowel preparation regime can reduce both patient anxiety and the burden on the healthcare system.

BOX 3.1 Advantages of a successful bowel preparation regime

Speeds diagnosis

Improves specificity and sensitivity

Helps limit investigation to a single examination

Means shorter examination times, which can minimize patient discomfort, allow higher throughput of patients, and minimize radiation dose to patients and staff

The more distal in the GI tract the examination, the greater the patient preparation required. Little or none is required for examinations of the salivary glands, larynx, pharynx or esophagus (when imaged alone). For imaging the esophagus and stomach, generally a few hours’ dietary restriction is all that is required.

For small bowel imaging, preparation varies by imaging modality. For a fluoroscopic examination of the small bowel, the patient may require a laxative the day before and to have nothing to eat or drink for approximately eight hours prior to examination. For other imaging procedures such as computed tomography (CT) enteroclysis and capsule endoscopy, preparation may be more intensive (Paulsen et al., 2006; Rajesh and Maglinte, 2006; Van Tuyl et al., 2007; Kalantzis et al., 2007).

There is no single ideal preparation regime for imaging of the small bowel and the colon, but the principal elements used are a combination of dietary restriction and a laxative bowel cleansing solution.

Psychological and physical considerations of patient preparation

The main colonic imaging examinations, including barium enema, colonoscopy and computed tomography colonography, require bowel preparation. Efficacy of the preparation needs to be balanced with patient compliance and acceptability in respect of taste, volume and action. It is not feasible to ‘tailor’ a bowel preparation regime for individual patients; therefore, a standard regime to suit most bowel habits is generally used. However, any regime adopted will only ever be as good as the patients’ ability to understand and willingness to carry out the instructions for taking it. Issues for patients taking colon preparations include the complexity of preparing it, the taste and volume to be taken and the physical effects it has on them (potentially, this includes nausea, vomiting, bloating, cramps, headache, urgency and loss of sleep) (Gluecker et al., 2003).

Patients may already be anxious because they have symptoms that have made them visit a doctor and the expectation of pain and embarrassment of an examination of the GI tract may add to this. Detailed but concise written instructions should be provided in lay language for patients, together with details of what happens during the examination. Ideally, these should also be explained by the referring clinician to ensure the full cooperation of the patient (Department of Health, 2001). Once home with the preparation and instructions, patients often find questions they wish to ask, so contact details for someone who can answer queries and provide reassurance are essential.

Timing of preparation can affect patient experience. In a study comparing a preparation regime given in the morning to one group and the same given in the afternoon to another group, the preparation had similar efficacy when assessed overall. However, when the right side of the colon alone was assessed, preparation was significantly better in the morning group; the afternoon preparation was associated with loss of more working hours and sleep (Gupta et al., 2007).

Patient referral for a GI examination should include consideration not only of the clinical appropriateness of the test, taking into account the symptoms and potential risks from the test, but also from the physical and psychological perspective. Patients need to be capable of following the instructions, so special thought must be given to patients with a learning disability, English as a second language, ethnic or religious reasons why they may not be able and/or willing to undergo the examination after taking the prep (e.g. Muslim women wearing x-ray gown – male health professional undertaking the examination).

Physical barriers to complying with either the preparation or examination include immobility and incontinence, which can cause poor tolerance of bowel cleansing. Likewise strict dietary and purgative preparations in conditions such as diabetes could have serious consequences if not appropriately addressed. For elderly patients and those with diabetes, special effort should be made to ensure an early morning appointment and/or additional dietary advice to avoid adverse events such as dehydration and/or hypoglycemia (Lichtenstein et al., 2007). For example, patients with diabetes are advised that the clear fluids they drink should be sugar free and that they should check their blood sugar levels more frequently than usual. Elderly patients without home support or at risk of adverse effects from the preparation and those with learning difficulties may have to be admitted to a hospital ward for supervision. It should be noted, however, that in-patient preparation is often poorer than that of out-patients (Hendry et al., 2007).

Where a perfectly clean colon is the goal, it is not always achieved in all patients, so the presence of fecal matter has to be recognized at the time of the examination and, if necessary, the technique modified and extra views taken. Where fecal residue renders an examination suboptimal, the reporter needs to state this and the level of confidence they have in their findings, so the referring clinician can follow up patients appropriately. Occasionally, the preparation may be so poor that the examination has to be abandoned and the patient referred for re-preparation. This should not be taken lightly and detailed discussion with the patient to establish possible causes for failure of the preparation are essential, especially where there is fecal impaction. It has been known for patients to be re-prepared a couple of times, before a stricturing lesion is found. This increases the risk of perforation, a delayed diagnosis or an acute presentation for obstruction, reducing the chances of a favorable outcome (Centre for Reviews and Dissemination, 2004). In all such cases the anxiety, discomfort, inconvenience and risk of repeated preparation for the patient should not be underestimated; their general physical and mental wellbeing should also always be taken into consideration.

Minimal preparation CT (MPCT) colon was introduced in the early 1990s in the UK (Koo et al., 2006; Ganeshan et al., 2007). Understandably, patients prefer examinations that require less bowel preparation, and minimal preparation techniques in both CT and MR colonography have been developed (Florie et al., 2007; Tolan et al., 2007; Taylor et al., 2008). While these examinations may be suitable for the elderly and frail where evidence of large and structuring lesions is sought, they are far less reliable for detection of smaller lesions and polyps.

MRI colongraphy is a rapidly developing area of colon imaging and this is reflected in the variety of preparation regimes being used. The principles are similar to those used for CT colonography; however, the emphasis is on the use of fecal tagging with or without a cleansing agent. Minimizing the preparation required is a focus of current developments (Pickhardt, 2007; Kuehle et al., 2007; Taylor et al., 2008).

Contrast media

All medical imaging techniques work by detecting the differences in the physical properties of tissues within the body. Contrast media are used to accentuate those differences and enhance the detail on the resultant image. The ideal contrast medium is one that can be safely administered, does not alter the patient’s physiology and only accentuates the tissues or organ specifically required.

Different contrast media are used with different imaging modalities. In x-ray examinations such as fluoroscopy and CT, positive contrast media are used. These contain elements with high atomic numbers, such as iodine and barium, and therefore absorb x-rays. Negative contrast media, such as air, may also be used to allow penetration by the x-rays. Occasionally, a combination provides the optimum imaging; for example, double contrast barium enemas involve the use of a positive (barium sulfate) and a negative (air or carbon dioxide (CO₂)) contrast agent to coat and distend the mucosal lining of the bowel which could not otherwise be seen. For CTC, in addition to the use of a contrast agent for fecal tagging and air or CO₂ to demonstrate the colon, intravenous iodinated contrast medium may also be used to highlight extracolonic structures (Tolan et al., 2007).

It is important to select the appropriate contrast media for the technique and area to be visualized, taking into account the contraindications associated with the contrast agent and any physical limitations on the part of the patient (e.g. age, morbidity) and compatibility with other agents used (e.g. laxatives for bowel preparation) (Bartram, 1994).

Positive contrast media

Water-soluble contrast media are iodinated organic compounds, particularly tri-iodinated benzene compounds, where iodine content is directly proportional to their radiodensity. While iodine content is related to effectiveness, safety is related to the osmolality of the solution, i.e. the number of particles present in a given weight of solution. The lower the osmolality, the less likely a reaction.

Water-soluble contrast media are classed as ionic or non-ionic, monomeric or dimeric and it is these properties that influence their use. Ionic monomeric media generally have a high osmolality, while non-ionic dimeric media have a low osmolality. For safety reasons, ionic contrast media are no longer in use; the incidence of severe reactions with non-ionic agents is 0.04% and very serious reactions is 0.004% (Katayama et al., 1990; Christiansen, 2005).

Administration and distribution within the body depend on the pharmacokinetic and physical properties of the individual contrast medium and are influenced by the viscosity, which is linked to the osmolality. Examples of contrast media in use for the imaging of the GI tract include iodixanol (Visipaque), a non-ionic dimeric, and iopromide (Ultravist), a non-ionic monomeric.

Intravenous iodinated contrast media should be used for the relevant licensed purpose and in line with the manufacturers’ recommendations. The complications and adverse effects from the use of contrast media, particularly when administered intravenously, range from nausea and vomiting to anaphylactic shock. Patients considered at increased risk of an adverse event are listed in Box 3.2. Identifying these patients prior to examination allows preventative action such as prophylaxis or use of an alternative examination not requiring iodinated contrast media (Royal College of Radiologists, 2005; Tramèr et al., 2006). Use in patients who are pregnant, hyperthyroid or receiving interleukin-2 treatment should be avoided; however, there are no special precautions.

BOX 3.2 Patients at increased risk of an adverse event following the administration of intravenous contrast agents

History of contrast media reaction

Multiple allergies

Documented severe allergy requiring therapy

Asthma

Those taking metformin

Impaired renal function

Diatrizoate meglumine (Gastrografin) is a water-soluble contrast medium that can be taken orally or given rectally for GI examinations. Its hyperosmotic properties mean it will draw fluid into the bowel lumen, which may be useful in patients who are constipated, but dangerous for patients presenting with a small bowel obstruction. It can also cause severe chemical pneumonitis if aspirated.

Barium sulfate preparations for the GI tract have to be of the right viscosity to wash residual mucus and food/fecal residue from the surface wall, but still be able to absorb residual fluid and adhere to the mucosal surface for the time the examination takes, without flocculating (clumping). It has to be radiopaque enough to demonstrate the mucosal detail; too dense and it could obscure lesions (Rubesin et al., 2000). There is a large range of preparations available either in powder or suspension form, with varying densities and with a variety of additives, such as suspending agents to ensure uniform coverage, dispersing agents to prevent bubble formation and flavors and sweeteners for products administered orally.

The use of barium sulfate is contraindicated in patients with gastrointestinal obstruction or perforation and should be avoided in those at risk of perforation (e.g. acute ulcerative colitis, post radiotherapy). The presence of barium sulfate in the abdominal cavity (e.g. perforation of the bowel) can lead to peritonitis, adhesions, granulomas and a high mortality rate (Sweetman, 2007). Although barium sulfate itself is inert, a range of hypersensitivity reactions to the additives contained in the preparation have been reported (Janower, 1986). Aspiration can lead to pneumonitis or granuloma formation (Sweetman, 2007).

Possible adverse effects following the administration of barium sulfate can include constipation and impaction, on occasion leading to fecoliths and appendicitis.

Barium sulfate is the preferred medium for the GI tract as it is safe, dense, giving good quality imaging, and is less expensive than iodine-based media. The use of water-soluble agents is indicated where barium sulfate is not feasible or is potentially dangerous.

Pain relief: antispasmodics, sedation and local anesthetics

Antispasmodics can be used to reduce both gut motility and patient discomfort during examinations that require distension, such as endoscopy, barium meal, barium enema and CTC. Hyoscine-N-butylbromide, Buscopan, is the most commonly used antispasmodic in the UK (NB it is not licensed for use in the USA). The contractions of the smooth muscle of the bowel wall are caused by a neurotransmitter called acetylcholine. These contractions are not under conscious control and are not usually felt but, if the muscles go into spasm, this can cause pain. Hyoscine stops the spasms in the smooth muscle by blocking the muscarinic or cholinergic receptors on the muscle cells that the acetylcholine would normally act on. This reduces the contractions, allows the muscle to relax and reduces the painful spasms and cramps. Hyoscine-N-butylbromide may cause temporary blurring of vision and cause the patient to have a dry mouth. Use is contraindicated in patients with closed angle glaucoma and should be avoided in patients with porphyria (Sweetman 2007; British Medical Association and the Royal Pharmaceutical Society of Great Britain 2008). Patients should be warned of the small possibility of exacerbating undiagnosed acute angle closure glaucoma. This is a very rare occurrence, but if they experience a pain in the eye, haloes around lights and blurred vision within 24 hours they must seek immediate medical attention. Buscopan can also increase the heart rate and caution should be used in patients with poorly controlled angina, heart failure or patients who are predisposed to tachycardia.

Glucagon is a polypeptide hormone identical to human glucagon that increases blood glucose and relaxes the smooth muscle of the gastrointestinal tract. Given intravenously, it is effective on the large bowel and, administered parenterally, it relaxes the smooth muscle of the stomach, duodenum, small bowel and colon (Eli Lilly, 2005). Glucagon is contraindicated in patients with known hypersensitivity to it and in patients with known insulinoma, pheochromocytoma or glucagonoma. Adverse reactions include nausea, vomiting, diarrhoea, hypokalemia (British Medical Association and the Royal Pharmaceutical Society of Great Britain, 2008). Where licensed for use, Buscopan is the preferred muscle relaxant as it is generally considered more effective and is considerably cheaper (Skucas, 1994; Rubesin et al., 2000).

The addition of peppermint oil to barium sulfate suspension has been shown to relieve spasm during barium enema and may be considered a simple, safe and cheap approach to reducing the number of patients who need to be given an intravenous antispasmodic agent (Sparks et al., 1995).

Sedation is commonly used during invasive GI procedures, such as endoscopy and stent placement. It relieves anxiety and causes temporary relaxation without putting the patient to sleep and has the advantage that most patients remember very little about the procedure afterwards. The type and dose of sedative given depends on the procedure and how anxious the patient is. The most common sedatives used are benzodiazepines, such as diazemuls or midasolam. Benzodiazepines work by acting on specific receptors in the brain causing the release of gamma aminobutyric acid (GABA). GABA is a neurotransmitter that acts as a natural ‘nerve-calming’ agent. It helps keep the nerve activity in the brain in balance, so as diazepam increases the activity of GABA in the brain, it increases its calming effect and results in sleepiness, a decrease in anxiety and relaxation of muscles.

With conscious sedation, it is sometimes possible for the patient to reach a deeper level of sedation than intended. For this reason, guidelines state that all patients should be monitored during conscious sedation, including their blood pressure, pulse and oxygen saturation (Royal College of Radiologists, 2003). The professional monitoring the patient’s condition throughout the procedure should have training in monitoring breathing and heart function. Immediate corrective action is necessary if sedation becomes too deep. Anexate injection contains the active ingredient flumazenil, which reverses the effects of benzodiazepines by competing with them for the GABA receptors. Flumazenil binds to the receptors, preventing benzodiazepines from acting on them. This blocks their effects and causes sedation to be reversed.

Sedative drugs do not block the pain signals to the brain, so local anesthesia may be given as well, for example, during a percutaneous transhepatic cholangiogram (PTC). Local anesthetics, such as lidocaine, are used to numb the skin and generally are administered by injection superficially under the dermis, then deeper into tissue depending on requirements of the procedure.

In addition to any preparation required for the specific GI procedure, patients requiring sedation should be asked not to eat for six hours before the procedure. After the procedure patients are usually allowed to go home once most of the effects of the sedation have worn off. However, they are advised not to drive, drink alcohol, operate machinery or sign legal documents for at least 24 hours after the treatment.

The use of sedation and local anesthetics is common practice and is generally safe, however, after sedation, patients may get a headache, feel nauseous or be sick, and have feelings similar to those of a hangover. Most people have some amnesia about the procedure but, on rare occasions, can have unpleasant memories of the procedure. There is a very small risk of an unexpected reaction to the anesthetic (British Medical Association and the Royal Pharmaceutical Society of Great Britain, 2008; US FDA, 2008).

Prescribing, supplying and administration of drugs

Bowel preparations, contrast media and antispasmodics are classified as non-controlled prescription only medicines (POMs). Originally, only medically qualified professionals could prescribe POMs but, in recognition of the expertise and value of advanced roles of nurses and allied health professionals, prescribing rights have been extended (Medicines Act 1969; Department of Health, 1999, 2000). In particular, provision has been made for persons who are operators under the Ionising Radiation (Medical Exposure) Regulations 2000 (IRMER) to administer POMs given in connection with medical exposures under those regulations (SCoR, 2001; Department of Health, 2006).

In addition to writing a prescription (a legal document authorizing supply of a drug for a specific reason to a specific person), prescribing involves the supplying of a drug (by the pharmacy to the health professional or by a health professional to the patient) and the preparation and administration of a drug (whether self-administered by the patient or given by a health professional). These are separate actions and each should be undertaken within legislative and safety regulations. In order to confirm that local practice is safe and legal for everyone’s benefit, it is necessary to consider each action for every examination. Having mapped this information, it is important to ensure that the appropriate personnel, who are trained and competent, are undertaking those actions and that any delegated responsibilities are appropriately documented.

Non-medical prescribing is complex and governed by legislation particular to each country. A range of non-medical prescribing models has been introduced internationally and interpretation may vary depending on local conditions (Emmerton et al., 2005). In the UK, Patient Group Directions (PGD) are written instructions for the supply or administration of a licensed medicine/s in an identified clinical situation, where the patient may not be individually identified before presenting for treatment (NeLM, 2008). PGDs are drawn up locally, to identify the situation and drugs covered, those permitted to operate under it, and the training, updates and monitoring of practice required (Department of Health, 2005; MHRA, 2008). Another model, used widely in the USA, is prescribing by protocol, where authority is formally delegated by a medical prescriber. The protocol gives explicit details of the activities that may be performed by the person receiving the delegated authority. Other models used in the UK are that of supplementary prescribing, which relates to a patient specific clinical management plan, and independent prescribing; there is currently no role for either of these in diagnostic radiography.

Non-medical prescribers need to be trained in the appropriate use, properties, adverse effects and contraindications of the pharmaceuticals they are prescribing; have an understanding of the legal framework they are working within; understand their accountability and responsibilities; understand the level of consent required, how to obtain that consent and the information the patient must be given. Once trained, non-medical prescribers are also required to work within the PGD or protocol and keep a record of their competence (MHRA, 2008; NeLM, 2008; NPC, 2009).

Any Patient Group Directions or protocols should be mutually agreed between the delegating prescriber and the non-medical prescriber. It should be within the skills of the health professional, who must act only within their own area of expertise and competence. The documentation must be signed by the delegating medical prescriber and the health professional involved and approved by the pharmacy and organization in which it is to be used, to ensure appropriate organizational insurance indemnity.