What is the evidence for use of water as an effective contrast medium? What are the specific procedures where there is evidence of noninferiority with the use of water?

What is the evidence for use of water as an effective contrast medium? What are the specific procedures where there is evidence of noninferiority with the use of water?

Comment by InpharmD Researcher

Literature indicates that water has been used successfully as an oral contrast medium in coronary angiography/angioplasty and various types of abdominal imaging. Typically comparisons were made to a positive oral contrast agent without a specific procedure where water is non-inferior to oral contrast agents. According to the 2010 European Society of Urogenital Radiology (ESUR) guideline, water (750-1000 mL) can be utilized as an alternative to diluted oral contrast media, to be taken 1 hour before CT imaging for ovarian cancer staging. Please refer to Tables 1-4 for the summary of the primary literature.

Background

A 2010 guideline from the European Society of Urogenital Radiology (ESUR) presents 750-1000 mL of water as an alternative to diluted oral contrast media, to be taken 1 hour before CT imaging for ovarian cancer staging. Water functions by creating differentiation of bowel loops from calcifications. Still, the use of an additional intravenous contrast medium is also mandatory for staging. Substantial evidence supporting this practice was not provided. [1], [2]

A 2008 review described CT urography for evaluation of the urinary tract. Within the context of patient preparation, it was reported that up to 1,000 mL of water 20–60 min before CT has been used to improve delineation of ureteral segments and possibly facilitate diagnosis of incidental findings. Use of oral hydration with water was again distinguished from intravenous injection of contrast medium. [3]

Literature Review

A search of the published medical literature revealed 4 studies investigating the researchable question:

What is the evidence for use of water as an effective contrast medium? What are the specific procedures where there is evidence of noninferiority with the use of water?

Please see Tables 1-4 for your response.

Comparison of oral and intravenous hydration strategies for the prevention of contrast-induced nephropathy in patients undergoing coronary angiography or angioplasty: a randomized clinical trial
Design	Randomized clinical trial N= 120
Objective	To evaluate the clinical effectiveness of oral hydration with neutral water in the prevention of contrast-induced nephropathy (CIN) in patients undergoing coronary angiography or percutaneous coronary intervention (PCI)
Study Groups	Group A: intravenous (IV) hydration (n= 40) Group B: 500 mL oral water (n= 40) Group C: 2,000 mL oral water (n= 40)
Inclusion Criteria	Age 18-80 years, scheduled for coronary angiography or PCI, normal renal function, and baseline serum creatinine (SCr) below 110 µmol/L
Exclusion Criteria	Acute myocardial infarction, left ventricular dysfunction with a left ventricular ejection fraction below 45%, blood electrolyte disturbances, or liver dysfunction
Methods	Patients were randomized to one of three treatment groups. Group A received an intravenous (IV) infusion of normal saline at 1 mL/kg/h, initiated 12 hours before the procedure and continued for the next 24 hours after completion of coronary procedures. Group B consumed 500 mL of tap water 2 hours before the procedures, and another 2,000 mL over the 24 hours following the procedures. Group C consumed 2000 mL of tap water only within the first 24 hours after the procedure. Iopromide, a low-osmolality ionic contrast agent was used in all procedures, with adjunctive therapies left to the discretion of attending cardiologists.
Duration	January 2010 to October 2010 Median follow-up: 6.1 ± 2.2 months
Outcome Measures	Incidence of CIN, renal function
Baseline Characteristics*		Group A: IV hydration (n= 40)	Group B: 500 mL oral water (n= 40)	Group C: 2,000 mL oral water (n= 40)
	Age, years	55.7 ± 11.9	57.2 ± 9.2	54.9 ± 10.8
	Male	22 (55%)	21 (53%)	24 (60%)
	Medical history Hypertension Diabetes Previous MI Prevous PCI	7 (17%) 10 (25%) 4 (10%) 5 (12.5%)	8 (20%) 9 (23%) 3 (7.5%) 6 (15%)	6 (15%) 11 (27%) 5 (12.5%) 5 (12.5%)
	Cardiac angiography procedure Coronary angiography only Coronary angiography and ad hoc PCI	13 (32.5%) 27 (67.5%)	14 (35%) 26 (65%)	15 (37.5%) 25 (62.5%)
	MI, myocardial infarction *There was no statistically significant difference at baseline between the groups (p> 0.05).
Results	Endpoint	Group A: IV hydration (n= 40)	Group B: 500 mL oral water (n= 40)	Group C: 2,000 mL oral water (n= 40)	p-value
	CIN	2 (5.0%)	3 (7.5%)	2 (5.0%)	0.86
	Renal function 3 days after SCr, µmol/L CrCl, mL/min BUN, mmol/L	108 ± 25.22 89 ± 16.4 6 ± 2.89	112 ± 23.66 99 ± 21.3 9 ± 3.09	107 ± 27.65 94 ± 19.3 6 ± 4.09	1.03 0.55 0.83
	Renal function parameters were followed at baseline, 12 hours after, 2 days after, and 3 days after. While there was a small increase in SCr within 12 hours following procedures, no parameter reached clinical significance at any time point. SCr, serum creatinine; CrCl, creatinine clearance; BUN, blood urea nitrogen
Adverse Events	See 'Results' section above.
Study Author Conclusions	This randomized clinical trial showed that the prevalence of CIN in patients who received oral hydration was similar to that in patients treated with intravenous saline infusion. These results suggest that hydration with oral fluids before and after coronary angiography or PCI may be as effective as an intravenous saline infusion in preventing CIN in patients undergoing coronary angiography or PCI.
InpharmD Researcher Critique	For the purpose of hydration, orally administered water was found to be similar in safety to IV normal saline. However, all patients were still administered an ionic contrast agent. Additionally, the volume of oral water as a potential contrast still remains unclear.

References:

Kong DG, Hou YF, Ma LL, Yao DK, Wang LX. Comparison of oral and intravenous hydration strategies for the prevention of contrast-induced nephropathy in patients undergoing coronary angiography or angioplasty: a randomized clinical trial. Acta Cardiol. 2012;67(5):565-569. doi:10.1080/ac.67.5.2174131

Water as neutral oral contrast agent in abdominopelvic CT: comparing effectiveness with Gastrografin in the same patient
Design	Retrospective review N= 206 scans of 103 patients
Objective	To make a head-to-head comparison of water as neutral oral contrast (OC) against gastrografin as positive OC for abdominopelvic computed tomography (CT) scans in the same patient
Study Groups	Water (n= 103 scans) Gastrografin (n= 103 scans)
Inclusion Criteria	Age ≥ 18 years, with at least two abdominopelvic CT scans with intravenous (IV) contrast done in the routine portovenous phase, one with gastrografin (prior to third quarter of 2011) as positive OC and other with water as neutral OC (after third quarter of 2011)
Exclusion Criteria	No CT scans with both water and gastrografin, age < 18 years, CT scan done in emergency department (ED), scans without IV contrast, scans with specific protocols (such as liver or pancreatic multiphasic protocol, CT enteroclysis)
Methods	Prior to CT scan, each patient was administered 70-90 mL of IV iodinated contrast at 1.5 to 2.0 mL/s. Contrast-associated artifact was graded based on extent of streak artifact from adjacent high-density contrast and whether they affected organ visualization. Small bowel wall delineation was graded based on ability to visualize wall separate from the intraluminal contents and the ability to appreciate the mucosal folds. A five-point scale was used for each parameter (1 = whole organ is not visualized, 2 = less than half the organ visualized, 3 = about half the organ visualized, 4 = more than half the organ visualized, 5 = whole organ visualized).
Duration	Scan performed from January 1, 2008 to December 31, 2011
Outcome Measures	Visualization of each abdominopelvic organ, contrast-associated artifacts, and small-bowel wall delineation
Baseline Characteristics		All patients (N= 103)
	Age, years Median 20-39 40-59 60-79 > 80	62.9 7 (6.8%) 33 (32%) 53 (51.5%) 10 (9.7%)
	Female	37 (35.9%)
	Time gap, months Median 1-3 3-6 6-9 9-12 >12	5 40 (38.8%) 17 (16.5%) 14 (13.6%) 8 (7.8%) 24 (23.3%)
	Reasons for referral Oncology patients Non-oncology patients	68 (66%) 35 (34%)
	Number of patients with small bowel pathology	76.6
Results	Endpoint	Water (n= 103)	Gastrografin (n= 103)	p-Value
	Overall visualization GI organs Solid organs Peritoneum	4.4 ± 1.2 4.3 ± 1.6 4.7 ± 0.58	4.3 ± 1.3 4.4 ± 1.6 4.8 ± 0.55	0.12 0.078 0.65
	Contrast-associated artifact GI organs Solid organs Peritoneum	4.6 ± 1.1 4.3 ± 1.6 4.8 ± 0.52	4.6 ± 1.2 4.3 ± 1.6 4.8 ± 0.51	0.65 0.78 0.72
	Small bowel subgroup analysis Overall visualization Duodenum Jejunum and Ileum Contrast-associated artifact Duodenum Jejunum and Ileum Wall delineation Duodenum Jejunum and Ileum	4.5±1.0 4.5±0.62 4.6±1.0 4.7±0.57 4.3±1.1 4.1±0.84	4.3±1.1 4.5±0.61 4.6±1.0 4.7±0.57 3.7±1.1 4.0±0.74	0.011 0.89 0.74 0.56 <0.001 0.22
Adverse Events	N/A
Study Author Conclusions	The study confirms that water as a neutral OC is comparable to gastrografin in terms of enabling visualization of abdominopelvic organs. This is in agreement with evidence in the literature. Moreover, comparing performance of the two OC agents in the same patient in our study gives a more accurate assessment. The authors suggest that water can be used in place of gastrografin as oral contrast in abdominopelvic CT without compromising scan interpretation.
InpharmD Researcher Critique	This study is advantageous due to both agents being evaluated in the same patient, however, the agents were administered at a median interval of 5 months apart. Again, in this study water was not replacing the IV contrast agent; all patients still received IV iodinated contrast.

References:

Lee CH, Gu HZ, Vellayappan BA, Tan CH. Water as neutral oral contrast agent in abdominopelvic CT: comparing effectiveness with Gastrografin in the same patient. Med J Malaysia. 2016;71(6):322-327.

A prospective study comparing water only with positive oral contrast in patients undergoing abdominal CT scan
Design	Single-center, prospective, non-randomized case-control study N= 320
Objective	To compare the image quality rating, diagnostic confidence per structure in the abdomen, overall diagnostic confidence to address the clinical question, and radiation exposure between water only and positive contrast (Télébrix Gastro diluted in water) as an oral contrast agent in outpatients undergoing abdominal computed tomography (CT)
Study Groups	Water only (n= 233) Positive oral contrast (Télébrix Gastro) (n= 87)
Inclusion Criteria	Aged ≥18 years; scheduled to undergo an abdominal CT scan (with or without neck and chest scan) with oral and intravenous contrast; outpatients
Exclusion Criteria	Undergoing CT for research purposes; not able to drink; requiring positive oral contrast for evaluation of the gastrointestinal/intraluminal tract (primary staging and response monitoring of colon tumor, staging of inflammatory bowel disease, evaluation of anastomotic leaks, evaluation of gastrointestinal stromal tumor); patients with complex problems
Methods	Eligible patients underwent contrast-enhanced abdominal CT scans and were asked to choose between water only as oral contrast (1000 ml) or positive oral contrast (50 ml Télébrix Gastro diluted in 950 ml water), as both methods are generally accepted in the Netherlands. Those who chose water only were instructed to drink this volume in 45 minutes. The patients who chose positive oral contrast (50 ml Télébrix Gastro + 950 ml water) were instructed to drink within 60 minutes as standard protocol. CT scans were performed according to our routine protocol, using 4 different CT systems (two 64 slice systems, one 128 slice system, and one dual-source 2*192 slice system. Iomeron (300 mg I/ml) was used as the intravenous (IV) contrast agent. Two abdominal radiologists, with respectively 6 years (observer 1) and 19 years (observer 2) experience in evaluating abdominal scans, reviewed each image set independently.
Duration	June 2018 through September 2018
Outcome Measures	Radiation measures: Dosis Length Product (DLP), volume CT dose index (CTDI_vol); diagnostic confidence; image quality of the abdomen; palatability
Baseline Characteristics*		Water only (n= 233)	Positive oral contrast (n= 87)
	Age, years	62.7 ± 12.17	62.9 ± 13.78
	Female	103 (44%)	47 (54%)
	Body mass index, kg/m²	25.7 ± 5.00	25.4 ± 4.15
	Patient spectrum Oncology Hematology Others	200 (85.8%) 12 (5.2%) 21 (9.0%)	71 (81.6%) 10 (11.5%) 6 (6.9%)
	Region scanned Neck/chest/abdomen Chest/abdomen Abdomen	43 (18.5%) 147 (63.0%) 43 (18.5%)	23 (26.4%) 46 (52.9%) 18 (20.7%)
	CT scanner 64 slice scanners 128 and 2*192 slice scanner	202 (86.7%) 31 (13.3%)**	80 (92.0%) 7 (8.0%)**
	Not significantly different Due to the low number of patients scanned on the 128 and 2192 slice scanners, these data were combined.
Results	Endpoint	Water only (n= 199)	Positive oral contrast (n= 79)	p-value
	Median total DLP in milligray*centimeters (range) Neck/chest/abdomen Chest/abdomen Abdomen	775.4 (420.0 to 1383.6); n= 37 722.1 (327.3 to 1547.5); n= 125 509.5 (329.4 to 1563.0); n= 37	815.4 (407.9 to 1167.8); n= 21 725.6 (328.0 to 1442.4); n= 41 650.2 (279.8 to 1035.2); n= 17	0.994 0.877 0.703
	Median CTDI_vol in milligray (range) Neck/chest/abdomen Chest/abdomen Abdomen	9.11 (5.18 to 17.32); n= 37 10.53 (4.90 to 21.12); n= 125 10.31 (6.26 to 26.81); n= 37	9.51 (5.01 to 13.06); n= 21 10.27 (5.81 to 19.85); n= 41 11.40 (6.35 to 18.61); n= 17	0.815 0.863 0.485
	Diagnostic confidence (number with "less than good rating") Gastrointestinal system Peritoneum Retroperitoneum Lymph nodes	18 (7.7%) 21 (9.0%) 11 (4.7%) 11 (4.7%)	1 (1.1%) 1 (1.1%) 0 0	0.031 0.012 0.040 0.040
	The agreement between the observers for the evaluation of the diagnostic confidence was 97.5% (312/320). Although not statistically significant, Télébrix Gastro was more unpleasant for patients (n= 16, severe/mild/less than good) in comparison with water only (n= 12, severe/mild/less than good). There was no difference between the water only and positive contrast for both observer 1 and observer 2 (p-values were respectively 0.574 and 0.310).
Adverse Events	N/A
Study Author Conclusions	Abdominal CT with water only has comparable diagnostic confidence as abdominal CT with positive oral contrast in the majority of outpatients. Therefore, water only can replace positive oral contrast in the standard CT protocol for the majority of outpatients scheduled to undergo an abdominal CT.
InpharmD Researcher Critique	This study was limited based on the single-center and non-randomized design. The study suffered from selection bias as patients were allowed to choose contrast type with the majority choosing water. Moreover, the patient population mainly consisted of oncological patients and the results may not be generalizable to other patient populations.

References:

de Wit PAM, Tielbeek JAW, van Diepen PR, Oulad Abdennabi I, Beenen LFM, Bipat S. A prospective study comparing water only with positive oral contrast in patients undergoing abdominal CT scan. Sci Rep. 2020;10(1):6813. Published 2020 Apr 22. doi:10.1038/s41598-020-63838-3

Small Bowel MRI: Comparison of a Polyethylene Glycol Preparation and Water as Oral Contrast Media
Design	Prospective, observational study N= 25
Objective	To compare water and a polyethylene glycol (PEG) preparation as potential oral contrast media for magnetic resonance imaging (MRI) of the small bowel
Study Groups	Water (n= 22) PEG (n= 22)
Inclusion Criteria	Healthy volunteers; no past history of bowel disease; underwent MRI small bowel examination at the same time of day on two separate occasions one week apart
Exclusion Criteria	Not specified
Methods	All eligible participants underwent two separate MRI examinations after drinking up to two liters of water (first examination), and after one week, PEG preparation (second examination). Small bowel images were obtained every 10 minutes for at least two hours using breath-hold single shot half-Fourier imaging, including both thick section projection and thin section images. Two radiologists in consensus, blinded to the volunteer and contrast details, evaluated examinations for arrival at the terminal ileum, transit time, and demonstration of small bowel segments via a five-point grading scale. All examinations were performed using a commercial whole body MRI system.
Duration	Each examination: 3 hours
Outcome Measures	Mean subjective grading scores
Baseline Characteristics		All participants (N= 25)
	Age (range), years	21 to 55
	Female	10 (40%)
		Water (n= 22)	PEG (n= 22)	p-value
	Liquid volume, mL	1120 ± 110	950 ± 90	0.01
	Drank full 2 liters	8 (32%)	6 (24%)	-
	Liquid reached the terminal ileum	14 (63.6%)	21 (95.5%)	0.04
	Mean small bowel transit time, min	50.6 ± 48	37.7 ± 22	0.28
Results	Endpoint	Water (n= 22)	PEG (n= 22)	p-value
Results	Mean Subjective Grading Scores Duodenum I/II Duodenum III/IV Jejunum Ileum Terminal ileum	2.6 1.6 2.3 2.0 1.2	2.8 1.5 3.0 2.9 2.7	0.37 0.71 0.07 0.005 0.002
Adverse Events	N/A
Study Author Conclusions	The results presented confirm that the PEG preparation was similar to water for demonstrating the proximal half of the small bowel, but performed significantly better than water for demonstrating the distal half of the small bowel in volunteers.
InpharmD Researcher Critique	This study was limited by its small sample size and observational nature. Although PEG performed significantly better than water for demonstrating the distal half of the small bowel, water may still remain a potential alternative at times of shortage or when PEG palatability is an issue.

References:

Sood RR, Joubert I, Franklin H, Doyle T, Lomas DJ. Small bowel MRI: comparison of a polyethylene glycol preparation and water as oral contrast media. J Magn Reson Imaging. 2002;15(4):401-408. doi:10.1002/jmri.10090