1. Use and Safety Considerations
GI Contrast & Drugs
Use and Safety Considerations
Neil F. Wasserman, M.D.
Professor, University of Minnesota

2. Disclosure
I have nothing to disclose. Neither I nor any family member has any connection with imaging technology vendors or pharmaceutical companies.

3. Update on GI Contrast and Drugs
Details and references to be found in ACR Manual on Contrast Media

4. Update on GI Contrast and Drugs
Last update (v7) was in 2010 and was only 2 pages in length and not referenced!
Latest update (v9) in 2013 and is 17 pages long and fully referenced!

5. Topics of Discussion Oral Contrast Agents IV Contrast Agents
Barium
Thin (15-20% w/v)
High-Density ( % w/v)
VoLumen = 0.1% dilution
Iodinated
IV Contrast Agents
Ancillary Products & Drugs
Additives

6. Emphasis on Safe Use Allergies & Anaphylaxis
Non-idiosyncratic Reactions
Physiological
Side Effects

7. GI Studies Pharyngo-esophagraphy UGI Colon Small Bowel
Cholangio/Pancreatography
Sinography

8. Oral Contrast ACR Clarifying Statement*
Clarifying Information for MM.4.10 and Oral Contrast Media. The following information is being provided by the Joint Commission based on organizations’ requests for information about the applicability of Medication Management standard MM.4.10 to the administration of oral contrast agents. Contrast media are considered a medication. The administration of oral contrast media without prior pharmacist review has been determined to be safe, a standard of practice by pharmacists and the American College of Radiology, and acceptable to the Joint Commission. While review by a pharmacist before administration remains a recommended safety step, contrast media can be safely administered orally in an inpatient or outpatient setting as long as the following standards and safe guards are followed*:• The organization adopts clinical practice guidelines or approved screening tools to address the safe administration of contrast media (LD.4.20). In the case of hospitals, the clinical practice guideline or screening protocol must be approved by the medical staff and pharmacy.• Only trained, designated individuals retrieve medications from a limited set of medications (MM.4.50, EP 2)* Please note these standards are not limited to oral contrast media.• The appropriateness of the medication (contrast media) is reviewed by a health care professional determined to be qualified (MM.4.10, EP 3)• The organization implements quality control procedures to prevent retrieval errors (MM.4.50, EP 2)• A pharmacist is available on-call if needed (MM.4.50,EP 2)• Retrospectively, the organization evaluates its system by sampling records where contrast media were administered without prior pharmacy review to determine if the system as designed is working or if there are opportunities for improvement (MM.8.10). This does not include situations in which the pharmacy is sent an order to dispense a contrast agent to the inpatient floor for administration in non-urgent testing. In this situation, a review of the order is not only possible, but usually a part of the normal processing of medication orders by the pharmacist. In such cases, a review of the order is expected. For additional information regarding this standard and all other standard-related questions, please contact the Joint Commission’s Standards Interpretation Group at 630/ ▲
* ACR Web Site

9. ORAL CONTRAST Clarifying the Clarifying Statement
You may want to have a hospital policy stating that oral contrast is a “safe” drug and can be administered under a radiologist’s supervision without a written prescription to the pharmacy.
All contrast agents, products, and drugs should be reconciled with the electronic or paper record and through pt. questionnaire.

10. Oral & Rectal Barium (Barium Sulfate)
Uses
Fluoroscopic
Pharyngoesophagrography
UGIs
Small Bowel examinations
BEs
Oro-nasogastric tube placements
CT Colography
CT/MR Enterography

11. Barium Sulfate “Insoluble” in GI Tract
Characteristics
“Insoluble” in GI Tract
Miniscule amts. of Barium Sulfate dissociate into free ions that can permeate the bowel mucosa.
May form toxic compounds
barium chloride
barium sulfide Poisons
barium carbonate
Trace amts. absorbed are unlikely allergens
Measurable trace amt. barium in many water supplies

12. Barium Toxicity
Unlikely with medical grade barium unless contaminated with industrial grade
Barium chloride, sulfide, or carbonate
There are case reports of poisoning with pharmaceutical grade barium
(Boyd EM & Able M, Canad Med Assn J, 1966;Savry C, 1999)
Physiol. Effect: absorbed barium causes electrolyte imbalance causing sudden severe hypkalemia, N&V, watery diarrhea ➞ severe mm weakness, resp. arrest, coma, cardiac arrythmia, and death.
Rx is aggressive potassium replacement and electrolyte monitoring.

13. Barium Adverse Effects
Allergy & Anaphylactoid Reactions
rare (1:750,000)
Additive related?
Other Complications
Leakage into mediastinum or peritoneum
Aspiration
Bacteremia (14-23% of BEs)
Side Effects (due to viscus distention?)
Nausea and Vomiting
Abdominal cramping
Vasovagal
Source of incidence allergy/analphylaxis: Gelfand, 1985 quoting E-Z-EM
Mild Allergic Rx include itching, urticaria, rash, and mild bronchospasm.
Moderate to severe Rx include extensive dermal responses, respiratory symptoms, severe vasovagal or hypotensive events, severe bronchospasm, and angioedema of stomach and small bowel.
Anaphylatic fatalities have been rarely reported with UGI and Colon studies (Janower,1986; Harrington, 1987; Feczko,1989 & 1990; Gelfand, 2005).
Most additives assoc. with allergy have been removed from barium by the manufacturers, e.g. chocolat, citrus, and some other “natural” flavorings. However, much is unknown regarding additives as they are proprietary and FDA does not require listing on lablels or advertising if they are deemed generally “safe” by the FDA. Methylcellulose is probably left in.
Leakage into the mediastinum
Leakage into the peritoneum associated with peritonitis, death.
Aspiration assoc. with pulm. Edema, granuloma formation, death.
Bacteremia proven with oral and rectal contrast
Adverse Side effects mild-moderate and transient. Related to bowel distention

14. Barium Additives Allergy
GRAS (generally regarded as safe by FDA)
Found in foods, cosmetics, pharmaceuticals
Antifoaming agents e.g. dimethyl polysiloxane
Flavoring agents e.g. chocolate & citrus
Both are known allergens
Preservative stabilizers e.g. carrageenan
Antiflocculants
Carbomethylcellulose
Improves coatiing and flow (known allergen)
Methyl cellulose is a known allergen.
9% of a population screened for IgE carboxymethylcellulose-specific antibodies were positive. Of these, 1.6th were strongly positive (1.6A% of total population tested). (Muroi N. NEJM, 2002).
Positive skin testing to carboxymethylcellulose in pt. with anaphylaxs following UGI (Muroi N, NEJM, 1997)

15. Methylcellulose
9% of population have high titers to carboxymethylcellulose-specific IgE antibodies (Muroi N. NEJM, 2002)
Probably sensitized from CMC additives in foods, drugs, cosmetics, etc.
Pos. skin test to CMC in a pt. with anaphylaxis following UGI (Muroi, H. NEJM, 2007)

16. Barium Leak into Mediastinum
Mediastinitis
More intense in presence of bacteria
(Ginai AZ, et al.Experimental evaluation of various available contrast agents for use in the upper gastrointestinal tract in case of suspected leakage. Effects on mediastinum. British Journal of Radiology , )
Sepsis
Mortality rate = 22%
(Duranceau A. in Sabiston DC Jr, Lyerly HK (eds.) Textbook of Surg. WB Saunders, 1997, ed 15, p 267)
Survivors
Granuloma formation
Poor Reabsorption s/Redisual Barium

17. Barium Leak into Peritoneum
Peritonitis
2-8/10,000 Barium Enemas
(Ott DJ. JAMA, 1983)
Barium alone ➜ inflammatory reaction
Barium plus intestinal contents is worse
(Ginai AZ. Br. J Radiol 1985;58: )
Severity increases when leak is from lower intestinal tract due to higher associated bacterial count (Karanikas ID. Postgrad Med J 1997)
Mortality approaches 50%

18. Aspiration of Barium
Large aspiration leads to pulm. Inflammation and occasionaly death
Significant risk is in infants and elderly with advanced COPD and other lung disease in pts. with little reserve.
(Fruchter O, NEJM,2003;Tamm, Respiration, 1999; Lopez-Castilla JD. Pediatr Pulmonol, 1997;Ginai AZ, Br J Radiol, 1984; Gray C, Clin Radiol, 1989)

19. Iodinated Contrast Oral IV
Gastrografin (diatrioate meglumine- diatrizoate sodium)
Gastroview (diatrizoate meglumine- diatrizoate sodium)
Hypaque (diatrizoate sodium)
Omnipaque (Iohexol) (nonionic)
Oragrafin, Telepaque (Iopidic acid) IV
Cholografin (Iodipamide meglumine)
Isovue (Iopamidol meglumine)
Gadolinium

20. Oral Iodinated Contrast
Fluoro GI Uses
Pharyngo-esophagography
UGIs
Small Bowel Studies
SBFT
Enteroclysis
Enterography
BEs
Sinograms/Fistulograms

21. IV Iodinated Contrast CT/MRI of Abdomen & Pelvis CT/MR Enterography
“Advanced” GI Uses
CT/MRI of Abdomen & Pelvis
CT/MR Enterography
CT Cholangiography
CT/MR Cholangiopancreatography
CT Colography (CTC)

22. Iodine Oral Administration Intravenous Allergy/Anaphylactoid Rctn.
Rare and mild to moderate
Other Complications
Oral Administration
Aspiration
Bacteremia
Side Effects
Intravascular
Allergy/Anaphylactoid Rctn.
Anaphylactic rare
Allergy uncommon
Other Complications
Contrast Extravasaton
Nephrotoxicity? for IV
Nephrogenic Syst. Fibrosis

23. Iodinated Contrast Adverse Effects
Oral
Allergy
1-2% of oral iodinated contrast is absorbed and excreted by the kidneys (Rosen RS,1965;Eisenberg RL,1979)
Absorption ⬆several fold w/inflammed mucosa (Marinelli DL,1987;Halme L,1995;Miller SH,1997)
Moderate to severe allergy is rare.

24. Iodinated Contrast Adverse Effects
Oral
Aspiration of Iodinated Contrast
In fluoroscopic doses in “at risk” patients, potential complication of pulmonary edema
(Reich SB, Radiology, 1969;Chiu CL,Radiology, 1974, McAllister WH, AJR, 1982; McAllister WH, Pediatr Radiol, 1984;Gimai AZ., Br K Radiol,1986)
This includes LOCM nonionics
Laboratory studies suggest nonionic contrast is least harmful (McAllister)
Despite this “evidence” there are many experienced GI radiologists who have never seen a significant complication from aspiration of either water-soluble contrast or barium.
Unless water-soluble contrast is followed by barium, up to 50% of perforations and anastomotic leaks will be missed
(Swanson J and Levine MS, AJR, 2003)

25. Iodinated Contrast Adverse Effects
Oral
Bacteremia
Water-soluble contrast in sick pts. may irreversibly damage intestinal mucosa and allow translocation of bacteria into the peritoneal cavity leading to sepsis (Feigenberg Z, Digestive Dis and Sciences,1994).
At least One of Three conditions must be present
Intestinal overgrowth of pathogenic organisms
Pts. on broad spectrum antibiotics
Pts. on antacids or H2 – blockers which lower the barrier for gastric acids
Pts. on prolonged parental nutrition ➜ intestinal mucosal atrophy
Disturbance of the Immune System
Direct injury to intestinal mucosa e.g. with (hyperosmolar contrast)

26. Iodinated Contrast Adverse EffectsIV
Allergy/Anaphylaxis
In general, for LOCM freq. adverse reactions in adults = 2% - 7%
Serious reactions are rare, but much more common than for oral contrast = 0.1% -0.2%
Fatal anaphylaxis occurs in 1 per 170, 000

27. Ancillary Drugs Oral Products Oral & Parenteral Drugs Glucagon
Methylcellulose
Improves coating & flow of Ba
Polyethelyne Glycol (PEG)
Less absorption in ileum than water
Water
Milk
Sorbitol (hydrophilic agent)
Lactulose (hydrophilic agent)
Mucofalk (hydrophilic agent)
Locust bean gum (same)
Effervescent granules
Glucagon
Hypcyamine sulfate
Metoclopramide
Secretin

28. Adverse Effects Ancillary Products/Drugs
Oral
Parenteral
Lactulose
Sorbitol used instead today
Methylcellulose
Still used but rare allergies
Glucagon
Antispasmotic
Rare Sx when used in doses ≤ 1 mg
Hyoscyamine
Antispasmotic not used in US
Metoclopromide (Reglan)
Gastric & Intest. Stimulant of Motility
Adverse Reactions Rare
Don’t give in Pt. w/pheochromocytoma!!
Long-term use may ➜ Tardive Dyskinesia
Secretin
Used to increase flow in pancreatography
May exacerbate acute pancreatitis
Rare allergies
Flushing, vomiting, diarrhea, tachycardia, fever, blood clots

29. Recommendations Staff Awareness Contrast & Drug Reconciliation
Pt. Hx allergy, asthma, prior anaphylactoid reactions
Contrast & Drug Reconciliation
EMR
Paper chart
Every department should have a mechanism in place to evaluate and treat the rare adverse reactions to oral contrast or ancillary drugs.

30. Conclusion
GI oral and Intravenous contrast are among the safest products we use in medicine!