High-osmolality Contrast Agents Research Articles

Ratlarda intravenöz kontrast madde uygulamasının göz içi basıncı, göz yaşı miktarı ve oksidatif stres üzerine etkileri

Although iodinated radiocontrast agents, which are frequently used in radiological procedures such as indirect radiography, angiography, intravenous urography and computed tomography, are generally safe, they can cause serious side effects. In this study, it was aimed to investigate the effect of intravenous ionic high osmolar contrast agent administration on intraocular pressure, tear amount and oxidant and antioxidant parameters of eye tissue. Study groups consisted of 2 groups, Group 1 (Control) and Group 2 (Urographin), and a total of 16 Wistar albino female rats were used. On the first day of the experiment, 6 ml/kg of physiological saline was administered intravenously to the control group, and the same dose of contrast agent was administered to group 2. Intraocular pressure and tear amounts were measured at 1, 6, 12, 24 and 48 hours after intravenous administration. After measurements were made at the 48th hour of the experiment, all rats were euthanized and their eye tissues were removed. In order to reveal the oxidative damage and antioxidant activity in the eye tissue, malondialdehyde and reduced glutathione levels, catalase and glutathione peroxidase enzyme activities were measured spectrophotometrically. Schimer tear test (STT-1) strip was used for tear amount measurements, and rebound tonometer Tonovet® was used as tonometer for intraocular pressure measurements. No statistically significant difference was found between the control and urographin groups in terms of intraocular pressure and tear amounts in the measurements performed at 1,6,12,24 and 48th hours after urographin administration. It was observed that the same application significantly increased the malondialdehyde level (P<0.005) in the eye tissue. There was no significant difference between the groups in terms of reduced glutathione level and catalase and glutathione peroxidase enzyme activities in eye tissue. It was evaluated that intravenous contrast agent administration causes oxidative stress in the eye tissue and this may have a long-term ocular effect

Interventions for Promoting Meconium Passage in Very Preterm Infants-A Survey of Current Practice at Tertiary Neonatal Centers in Germany.

Meconium passage is often delayed in preterm infants. Faster meconium passage appears to shorten the time to full enteral feeds, while severely delayed meconium passage may indicate meconium obstruction. Neonatologists often intervene to promote meconium passage, assuming that benefits outweigh potential risks such as necrotizing enterocolitis (NEC). We performed an anonymous online survey on different approaches to facilitate meconium passage among tertiary neonatal intensive care units (NICUs) in Germany between February 2022 and April 2022. We collected information on enteral nutrition, gastrointestinal complications, and interventions to promote meconium passage. We received 102 completed questionnaires (response rate 64.6%). All responders used interventions to promote meconium passage, including enemas (92.0%), orally applied contrast agents (61.8%), polyethylene glycol (PEG) (46.1%), acetylcysteine (19.6%), glycerin suppositories (11.0%), and maltodextrin (8.8%). There was substantial heterogeneity among NICUs regarding frequency, composition, and mode of administration. We found no differences in NEC incidence between users and nonusers of glycerin enemas, high or low osmolar contrast agents, or PEG. There is wide variability in interventions used to promote meconium passage in German NICUs, with little or no evidence for their efficacy and safety. Within this study design, we could not identify an increased risk of NEC with any intervention reported.

In vitro analysis of the effect of contrast agents on the antiaggregant effects of P2Y12 inhibitors

ObjectivesThe contrast agents have different molarities and ionic structures. The high osmolar contrast agents could increase platelet aggregation but the ionic contrast agents decrease platelet aggregation. However there is insufficient data on whether the antiaggregan effect of P2Y12 inhibitors used during coronary interventions are affected by the contrast agents. This study aimed to evaluate the in vitro effects of different contrast agents on the antiaggregant activity of P2Y12 inhibitors (clopidogrel, ticagrelor and prasugrel). Materials and methodsThirty patients (who underwent percutaneous coronary interventions and were treated with a P2Y12 inhibitor for a minimum of 10 days) and five healthy volunteers were divided into four groups: the clopidogrel (10 patients), ticagrelor (10 patients), prasugrel (10 patients) and control (five volunteers) groups. Antiaggregant activity was measured by using the Verify-Now method and was represented as P2Y12 reaction unit (PRU) values. Three tubes of blood were collected from the participants in the three patient groups and in the control group; as the contrast material, 10% iohexol was added to a second tube, and 10% iodixanol was added to a third tube. PRU values of the control and the contrast tubes were measured at 5 min and at 30 min after the contrast material was added. ResultsIohexol and iodixanol led to a significant decrease in the PRU values in the control group (iohexol: 188.4 ± 39.2 vs 142.4 ± 17.0, p = .04; iodixanol: 188.4 ± 39.2 vs 159.2 ± 33.7, p = .04) and in the clopidogrel group (iohexol: 140.8 ± 50.8 vs 106.3 ± 44.4, p = .04; iodixanol: 140.8 ± 50.8 vs 109.4 ± 47.6, p = .009) but not in the ticagrelor and prasugrel groups. The PRU values were significantly lower in the ticagrelor (23.1 ± 26.2) and prasugrel (23.4 ± 27.5) groups than in the clopidogrel (140.8 ± 50.8) and control (188.4 ± 39.2) groups (p < .01), and the PRU values for the ticagrelor and prasugrel groups were similar for both the 5-min and 30-min time periods (p > .05). The antiaggregant activities of iohexol and iodixanol were observed to be similar at the 5- and 30-minute time points for all of the groups (p > .05). ConclusionIohexol and iodixanol had in vitro antiaggregant effects, and their antiaggregant effects were similar. Iohexol and iodixanol increased the clopidogrel antiaggregant activity in vitro, but they did not significantly alter the antiaggregant activities of prasugrel and ticagrelor.

Irreversible fatal contrast-induced encephalopathy: a case report

BackgroundContrast-induced encephalopathy (CIE) is a well-known complication of iodinated contrast agents during angiography and vascular interventions. It can manifest as hemiparesis, cortical blindness, speech changes, Parkinsonism, confusion, seizure, and coma. Most of the reported CIE cases have been transient and reversible. Irreversible fatal CIE cases have been rarely reported. All the fatal CIE cases reported involved the use of ionic high osmolar contrast agents. Here, we document a heretofore unreported fatal CIE after digital subtraction angiography (DSA) using iopamidol, which is a type of non-ionic monomer low osmolar contrast agent.Case presentationA 71-year-old woman was admitted to our Department of Neurology for tinnitus in the head. The cerebral magnetic resonance angiography (MRA) detected atherosclerotic cerebral arteries and bilateral stenosis of the middle cerebral arteries. The patient underwent DSA for further diagnostic work-up. The total amount of iopamidol used during the procedure was 110 ml. The patient experienced headache during the procedure, followed by dizziness with nausea and vomiting. Despite treatment with anti-oedema medications, her clinical status was gradually deteriorating and ended up with deep coma due to irreversible cerebral oedema which was confirmed by cerebral computed tomography (CT). Finally, the patient died 56 days after the procedure due to irreversible fatal cerebral oedema.ConclusionsThis report documents that iopamidol-induced encephalopathy may not always have a benign outcome and can result in irreversible fatal cerebral oedema.

STUDY OF SERUM NEOPTERIN, INTERLEUKIN-10 AND NEUTROPHIL TO LYMPHOCYTE RATIO IN CONTRAST INDUCED NEPHROPATHY

Background: Recent improvements in radio-diagnostic procedures and in cardiovascular percutaneous interventions, together with increased life expectancy, have resulted in the subjection of an increasing number of patients to contrast medium-enhanced examinations or cardiac and angiographic procedure requiring iodinated contrast medium injection.  Subjects and methods: This study was carried out at Internal Medicine, Cardiology, Radiology and Clinical Pathology departments, Zagazig University Hospitals. The study was approved by Institutional Review Board (IRB) and included a total of 60 patients.  Based on the development of contrast induced nephropathy after IV administration of high osmolar contrast agent, Patients were classified into CIN and NO CIN groups. We measured serum neopterin and IL-10 and calculating neutrophil to lymphocyte ratio before contrast administration, 24 and 48 hours after in 45 patients underwent coronary angiography for diagnostic and therapeutic purposes and 15 patients underwent renal angiography.  Results : About 25 % of the present studied patients (14 patients) fulfilled the criteria of contrast nephropathy with more cases in the percutaneous coronary angiography group (11 patients).This study revealed that serum neopterin, IL 10 and neutrophil to lymphocyte ratio were higher in patients with CIN following IV contrast media at 24 & 48 hours compared to patients without CIN. In our study; we found increased pre procedural and post-procedural CRP, ESR and uric acid levels at 48 hours in patients with CIN. We found a decreased basal serum total bilirubin level in patients with CIN following IV contrast media compared to patients without CIN.  Conclusion: Serum neopterin, IL 10 and neutrophil to lymphocyte ratio proved that they can be used as early biomarkers of contrast induced nephropathy instead of serum creatinine as they rise 24 hours before any change in the serum creatinine. Decreased serum total bilirubin levels had a higher incidence of CIN after the use of contrast media. Measuring ESR & CRP levels at admission may offer additional assistance in predicting the development of CIN. Elevated serum uric acid level is independently associated with an increased risk of CIN.  Abbreviations: CIN = Contrast induced nephropathy , AKI = Acute kidney injury, CRP = C-reactive protein, NLR = Neutrophil to lymphocyte ratio, ESR = Erythrocyte sedimentation rate, UA = Uric acid, eGFR = estimated glomerular filtration rate.  Keywords: Contrast induced nephropathy; Neopterin; IL-10; Neutrophil to lymphocyte ratio.

The Adoption of Low-Osmolar Contrast Agents in the United States: Historical Analysis of Health Policy and Clinical Practice

In this historical analysis of low- and high-osmolar contrast agents, we outline the reasons for the price depreciation, speculate on motivation for universal adoption by many radiologists despite suboptimal reimbursement, and cast light on important shortcomings of economic analyses in the realm of health policy. Early economic analyses regarding low-osmolar contrast agents concluded that universal adoption was not cost-effective. Over time, the price differential between low- and high-osmolar agents narrowed, yet reimbursement patterns lagged behind the narrowing price differential.

In vitro study of the antimicrobial effects of radiological contrast agents used in arthrography

Aspiration arthrography using an iodinated contrast medium is a useful tool for the investigation of septic or aseptic loosening of arthroplasties and of septic arthritis. Previously, the contrast media have been thought to cause false negative results in cultures when present in aspirated samples of synovial fluid, probably because free iodine is bactericidal, but reports have been inconclusive. We examined the influence of the older, high osmolar contrast agents and the low osmolar media used currently on the growth of ten different micro-organisms capable of causing deep infection around a prosthesis. Five media were tested, using a disc diffusion technique and a time-killing curve method in which high and low inocula of micro-organisms were incubated in undiluted media. The only bactericidal effects were found with low inocula of Escherichia coli and Pseudomonas aeruginosa in ioxithalamate, one of the older ionic media. The low and iso-osmolar iodinated contrast media used currently do not impede culture. Future study must assess other causes of false negative cultures of synovial fluid and new developments in enhancing microbial recovery from aspirated samples.

Contrast-Induced Acute Kidney Injury in Patients With Renal Dysfunction Undergoing a Coronary Procedure and Receiving Non-Ionic Low-Osmolar Versus Iso-Osmolar Contrast Media

BackgroundAlthough the superiority of low-osmolar over high-osmolar contrast agents in prevention of contrast-induced acute kidney injury (CI-AKI) is generally accepted, the relative nephrotoxicity of iso-osmolar over low-osmolar agents has not yet clearly defined. We examined the incidence of CI-AKI according to the type of contrast agent used in a randomized study of ascorbic acid for CI-AKI prevention. MethodsA total of 222 patients with baseline serum creatinine≥1.2mg/dL who were undergoing a coronary procedure and who were randomized to receive ascorbic acid or placebo were evaluated. The iso-osmolar agent iodixanol was used in 144 patients, whereas low-osmolar non-ionic agents were used in 78 patients (iomeprol, n=40; iobitridol, n=30; iopentol, n=8). CI-AKI was defined by an absolute serum creatinine increase of ≥0.5mg/dL or a relative increase of ≥25% measured 2 to 5days after the procedure. ResultsThe groups of patients who received iso-osmolar and low-osmolar non-ionic agents were well balanced in terms of demographic, clinical, and procedural characteristics. The overall CI-AKI incidence was 14.6% for the iso-osmolar iodixanol versus 14.1% for the combined low-osmolar non-ionic agents (iomeprol, 10%; iobitridol, 10%; iopentol, 50%). For iodixanol, the incidence of CI-AKI was 7.4% for patients randomized to receive ascorbic acid and 21.6% for placebo (P=0.02). The corresponding incidences for the low-osmolar non-ionic agents were 9.1% and 20.6%, respectively (P=0.19). ConclusionsNo differences in CI-AKI incidence were apparent among patients receiving non-ionic iso-osmolar iodixanol and non-ionic low-osmolar contrast agents. The preventative effect of ascorbic acid was also similar.

Subtle renal dysfunction after radiocontrast administration in prospective renal donors: Does N-acetylcysteine have a role in its prevention?

<b>Background: </b> Radiographic contrast media (RCM) can cause a reduction in the renal function by multiple mechanisms; reactive oxygen species is one of them. Whether the reduction can be prevented by the administration of antioxidants is still debatable. <i> N</i> -acetylcysteine (NAC) has shown some benefit in patients with renal dysfunction in the prevention of radiocontrast-induced nephropathy (RCIN). <b> Materials and</b> <b> Methods</b> : We prospectively studied 95 healthy kidney donors, who were undergoing intravenous urography (IVU) followed by digital subtraction renal angiography (DSRA) with ionic, high-osmolar contrast agent for pretransplant evaluation. Patients were randomly assigned either to receive the <i> N</i> -acetylcysteine 600 mg orally twice daily (acetylcysteine group) or placebo (control group) on the day before and that of RCM administration in addition to the intravenous 0.45% saline (1 ml/kg body weight per hour) on the day and following day of the procedure. Serum creatinine, urinary enzymes <i> N</i>-acetyl β glucosaminidase (NAG), γ glutamyl-1-transferase (GGT), alanine amino peptidase (AAP), fractional excretion of sodium (FeNa) and 24-h urinary creatinine clearance were performed before and 48 h after the procedure. The levels of urinary enzymes measured after 96 h of DSRA were available in only 57 donors. Radiocontrast-induced nephropathy was defined as an increase in the baseline serum creatinine of at least 0.5 mg/dl within 48 h after injection of radiocontrast media (RCM). <b> Results: </b> Increase in the urinary enzymes (NAG, GGT and AAP) and reduction in creatinine clearance was observed in both groups after receiving the contrast media. However, the number of patients with significant increase in enzymuria (at least >50% increase above the baseline value) and mean drop in creatinine clearance was statistically not different between the acetylcysteine and control groups. <b> Conclusion:</b> Renal damage in the form of reduction in creatinine clearance and increase in urinary enzymes has been observed after administration of radiocontrast. However, clinically significant RCM-induced acute kidney injury is uncommon in patients with normal renal function. Prophylactic oral administration of the antioxidant <i> N</i> -acetylcysteine at a dose of 600 mg twice daily before and on the day of contrast administration is probably not required in patients with normal renal function.

Bench-to-bedside review: Preventive measures for contrast-induced nephropathy in critically ill patients

An increasing number of diagnostic imaging procedures requires the use of intravenous radiographic contrast agents, which has led to a parallel increase in the incidence of contrast-induced nephropathy. Risk factors for development of contrast-induced nephropathy include pre-existing renal dysfunction (especially diabetic nephropathy and multiple myeloma-associated nephropathy), dehydration, congestive heart failure and use of concurrent nephrotoxic medication (including aminoglycosides and amphotericin B). Because contrast-induced nephropathy accounts for a significant increase in hospital-acquired renal failure, several strategies to prevent contrast-induced nephropathy are currently advocated, including use of alternative imaging techniques (for which contrast media are not needed), use of (the lowest possible amount of) iso-osmolar or low-osmolar contrast agents (instead of high-osmolar contrast agents), hyperhydration and forced diuresis. Administration of N-acetylcysteine, theophylline, or fenoldopam, sodium bicarbonate infusion, and periprocedural haemofiltration/haemodialysis have been investigated as preventive measures in recent years. This review addresses the literature on these newer strategies. Since only one (nonrandomized) study has been performed in intensive care unit patients, at present it is difficult to draw firm conclusions about preventive measures for contrast-induced nephropathy in the critically ill. Further studies are needed to determine the true role of these preventive measures in this group of patients who are at risk for contrast-induced nephropathy. Based on the available evidence, we advise administration of N-acetylcysteine, preferentially orally, or theophylline intravenously, next to hydration with bicarbonate solutions.

The effect of contrast material on transitional cell carcinoma viability.

In this study, increasing contrast concentration and/or exposure time decreased the growth and adherence of transitional cell carcinoma cells. Similarly, several authors have shown that the toxicity of contrast material to vascular endothelial cells in culture is related to concentration and time of exposure; this toxicity is minimized if non-ionic, low osmolar contrast is utilized. Identical trends of increasing toxicity with increasing osmolality have been documented with kidney cell lines, vascular smooth muscle cells, myocardial cells, neural cells, human fibroblasts, rat mesenchymal cells, and rat hepatocytes. The toxicity of contrast material in malignant cells (human cervical carcinoma cell lines and prostate cancer cell lines) has also been documented. Factors other than direct cellular toxicity may also affect the ability of malignant transitional cells transported with contrast material to implant on other sites in the collecting system. Zhan et al have evaluated neutrophil adhesion to contrast-exposed vascular endothelial cells. These authors observed increasing cellular adhesion with decreasing contrast dose. This was not related to osmolality as there was no similar endothelial adhesion activation with equal osmolality solutions of non-contrast solutions. The authors felt that contrast material, therefore, caused some form of modulation of cell adhesion molecules. This theory is supported by research by Owens et al that shows increases in the adhesive properties of endothelial cells to platelets after contrast exposure, and Rasmussen et al who found decreased granulocyte adherence with contrast exposure. In our study, transitional cell carcinoma cultures were placed on a collagen substrate to encourage adherence. There was an increasing number of non-adherent cells with increasing contrast concentration and exposure time, which suggests an effect of the contrast on cellular adhesion as well (Table 1). Potier et al found that rat mesangial cells were more sensitive to the cytotoxic effects of contrast agents than the less differentiated human fibroblasts were. This might suggest that the more poorly-differentiated transitional cell carcinoma cells would not be as sensitive to contrast material as low-grade tumors. However, we did not observe any differences in the responses of high- versus low-grade transitional cell tumors to exposure to contrast material. Intravenous contrast administration can lead to multiple adverse reactions, such as cardiotoxicy, nephrotoxicy, and hemodynamic toxicity. This makes non-ionic, low-osmolality agents preferable to ionic, high-osmolality agents. However, direct introduction of material into the urinary collecting system for the evaluation of transitional cell carcinoma may be less prone to seeding of viable malignant cells if ionic, high-osmolar contrast agents are utilized. Additional considerations include potential masking of very small filling defects in the upper urinary tract through opacification with extremely concentrated contrast material. Also, cytologic abnormalities are worsened by exposure to ionic, high-osmolar contrast agents, thus, any specimens for cytologic analysis should be collected prior to utilization of any contrast agents.

Adverse events with radiographic contrast agents: results of the SCVIR Contrast Agent Registry.

To determine prospectively the incidence of adverse events in angiography related to contrast agents, and the relative incidence of events with use of high-osmolality contrast agents (HOCAs) and low-osmolality contrast agents (LOCAs) and to ascertain if risk factors can help identify increased risk of an adverse event and patients likely to benefit from use of LOCAs. From 26 high-volume institutions, data were collected on every patient who underwent angiography from July 1, 1990, to June 30, 1992. Information included demographic and risk factors, general medical status, previous administration of contrast media, procedural information, occurrence and characteristics of all adverse events up to 12 hours after procedures, and relation to contrast agents, treatment, and outcome. In 60,891 patients, there were 75,616 studies, 56% with nonionic LOCAs, 8% with the ionic LOCA, and 36% with HOCAs. Most major risk factors correlated with an increased incidence of adverse events related to contrast media. Incidence of these adverse events varied with type of procedure, with a higher incidence associated with cardiac and interventional procedures. Overall adverse events related to contrast media and those for which treatment was necessary were significantly increased (P < .001) with use of HOCAs for all but arterial interventional procedures. Serious adverse events were not different between the two classes of agents except for cardiac procedures. Previous reaction to contrast medium was the most important risk factor in prediction of an adverse event. The safety benefit of use of LOCAs is limited. Patients most likely to benefit are those with a previous reaction or more than one other major risk factor. Selective use of LOCAs is an appropriate strategy.

The Unbearable Rightness of Bedside Rationing

A local internist is in the process of ordering an intravenous pyelogram for a patient she suspects of having kidney problems, when a medical student shadowing her in clinic interrupts. The student wants to know why the physician is not ordering a low-osmolality contrast agent for the patient, having read that they are less likely to cause serious side effects than high-osmolality contrast agents. The physician realizes that the medical student is correct, but rejects the suggestion, telling the student that "low-osmolality contrast agents are the standard of care for low-risk patients."

Rationing resources while improving quality

To the Editor. —In the September 14, 1994, issue of JAMA , Dr Eddy 1 uses three examples of increasing efficiency of utilizing limited health care resources. However, his first two examples, restricting mammography to more appropriate ages and changing the indications for cholesterol-reducing drug therapy, differ significantly from his third example, the use of high (HOCA) or low (LOCA) osmolar contrast agents balanced against the use of cervical cancer screening. In the first two examples, Eddy cites published scientific data to support a constructive and efficient reduction of overutilization of a single resource (mammography in the first case and cholesterol-reducing drugs in the second case), resulting in improvement in the quality of care, each for one specific illness. In his third example, however, the only resource common to both interventions is money; two unrelated illnesses are being balanced. He advocates administering HOCAs to all patients, even to those demonstrated to

Slip-ring and conventional dynamic hepatic CT: contrast material and timing considerations.

The major conclusions and recommendations of this review of contrast material use are summarized as follows: 1. Our recommendations for routine administration of contrast material are summarized in the Table. 2. Patient factors, such as weight, and liver and cardiovascular disorders may be taken into account when the above recommendations are modified. 3. Unenhanced scanning should be performed selectively. It is unnecessary for routine examinations performed with modern scanners and good contrast material injection techniques. 4. Although conclusive evidence is lacking regarding efficacy, reduced doses of contrast material may be given to patients with an elevated serum creatinine level. A full dose of low-osmolar contrast material may be given to functionally anephric patients if otherwise medically appropriate. 5. Differences in enhancement patterns produced by low-osmolar contrast agents and by high-osmolar contrast agents are small. Choice of contrast material should be based on other factors. 6. The dose of low-osmolar contrast material may be lower than the dose of high-osmolar contrast material so the examination cost may be reduced. 7. Low-osmolar contrast material is not satisfactory to use with delayed iodine scanning. 8. With use of slip-ring scanners and either helical or incremented scanning and recommended techniques, scanning should begin by the end of the injection of contrast material for biphasic techniques and within about 5-15 seconds after the end of injection for monophasic techniques. 9. Section thicknesses no greater than 8 mm should be used for helical or nonhelical scanning. 10. With helical scanning, a 1:1 pitch is preferred with a thickness of 5-8 mm. Overlapping sections may be used selectively to help identify and characterize small lesions. 11. Multiple-pass scanning is helpful to identify hepatocellular carcinoma in cirrhotic livers. This technique may also prove helpful in other conditions. As with any new technology, considerable advantages have come with new challenges, which can be overcome by knowing underlying principles and by attending to detail. Although we have learned much over the past 15 years about proper performance of abdominal CT examinations, we have much yet to learn about the effects of such examinations on the improved health of our patients and on the economic costs to society of providing this form of health care. Opinions on techniques have converged recently, as summarized herein. Therefore, we hope that some centers will now redirect their CT research toward the profoundly difficult, timely, and important issues of examination appropriateness, the value of quality improvement programs, clinical outcomes, and cost-effectiveness.

Coronary Microvascular Responses after Exposure to Iodinated Contrast Media

Iodinated contrast media can cause a number of well-described acute hemodynamic and vascular effects including vascular spasm, hypotension, and arrhythmias. Coronary microvessels were studied in vitro after high-dose exposure to an ionic, high-osmolar contrast agent diatrizoate meglumine in vivo. The aim of this study was to examine the endothelium-dependent and endothelium-independent vasodilator responses of the microvessels after previous contrast media administration in a clinically relevant setting. Left coronary angiography was performed on six pigs using a cumulative dose of 60 mL (5 mL/injection) of diatrizoate meglumine. After 1 hour of reperfusion, epicardial coronary microvessels were studied in vitro in a pressurized, no-flow state with video microscopy. The vasodilators bradykinin, calcium ionophore A23187, and sodium nitroprusside were sequentially applied extraluminally after preconstriction. Serotonin and the thromboxane A2 analog U46619 were studied without preconstriction. Microvessels exposed to diatrizoate meglumine had normal relaxation responses to the endothelium-dependent vasodilators bradykinin and calcium ionophore A23187 when compared to control vessels. The vasoconstrictor responses to U46619 and serotonin were not significantly altered compared to control vessels. Responses to the endothelium-independent vasodilator sodium nitroprusside were not reduced or were slightly enhanced after exposure to contrast media. Coronary resistance vessels responses to the endothelium-dependent vasodilators bradykinin and calcium ionophore A23187 are not diminished after previous exposure to diatrizoate meglumine. The vasoconstrictor responses to U46619 and serotonin were similarly unaffected by previous exposure to contrast media. This suggests that, when used in clinically relevant amounts, diatrizoate meglumine does not cause functional endothelium or vascular smooth muscle impairment.

Cost-effectiveness and safety of selective use of low-osmolality contrast media

We estimated our potential institutional savings by switching from universal to selective use of low-osmolality contrast media. A total of 42,598 radiocontrast studies (26,595 with high-osmolality contrast agents and 16,003 with low-osmolality contrast agents [LOCA]) were performed over 42 months. Every radiocontrast reaction was classified and documented. All costs associated with the subsequent treatment of adverse reactions were recorded and added to the cost of contrast agents. The actual cost of contrast agent administration was determined and compared with the theoretical cost of total conversion to LOCA. The overall rate of adverse reactions was 1.18%. The cost of radiocontrast materials and treatment of adverse reactions was $2,599,593. Over the same period, total conversion to LOCA would have cost $5,968,507. Our institution saved an estimated $962,548 annually through the selective use of LOCA. The incremental cost of treating adverse reactions associated with selective use was minimal compared with the cost of total conversion to LOCA.

Successful use of education and cost-based feedback strategies to reduce physician utilization of low-osmolality contrast agents in the cardiac catheterization laboratory

For the more than 1 million cardiac catheterizations performed in the United States annually, the cost of iodinated contrast agents is an important and potentially adjustable factor in overall cost. Low-osmolality contrast agents decrease the incidence of adverse effects, but are 15 to 20 times more expensive. Most adverse reactions to high-osmolality contrast agents are minor and generally do not prolong hospital stay or result in permanent injury. 1–4 A cost-effective solution would be to reserve low-osmolality agents for high-risk patients who are at greatest risk for contrast-related complications. 5–11 Implementation of strategies to promote cost-effective use of resources is often hampered by the difficulty of modifying physician behavior. Most studies looking at methods to alter physician-ordering behavior have been directed at the overuse of laboratory and radiographic tests. Educational strategies alone have a variable effect on test-ordering patterns of physicians. 12–14 Approaches in which physicians are given individual cost feedback information on practice patterns lead to a more consistent reduction in test utilization. 15,16 In this report, we examine the impact of education and cost feedback strategies to modify physician use of low-osmolality contrast agents for cardiac diagnostic and interventional catheterization procedures.

A comparison of low- with high-osmolality contrast agents in cardiac angiography. Identification of criteria for selective use.

Controversy exists as to whether low-osmolality radiographic contrast agents, which have less detrimental pharmacological effects but are considerably more expensive than high-osmolality agents, should be used universally or only for selected high-risk patients. A randomized, double-blind study was used to compare the frequency and severity of adverse events in 2245 consecutive patients undergoing diagnostic cardiac angiography. Two thousand one hundred sixty-six patients were successfully randomized to either iohexol, a low-osmolality contrast agent, or diatrizoate (as Hypaque 76), a high-osmolality agent. The end point event included clinically important adverse events (which jeopardized the patient or required aggressive treatment), contrast agent-related procedure abbreviations, and conversion to open-label contrast agent. Clinically important end point events were associated with increased age, New York Heart Association functional class, left ventricular end-diastolic pressure, arteriovenous oxygen difference, severity of coronary artery disease, and history of a previous reaction to contrast agent. End point events were less frequent in patients receiving iohexol (2.6% versus 4.6%; adjusted odds ratio, 1.59; 95% confidence interval, 0.97-2.60; P = .07). The difference in event frequency between iohexol and diatrizoate was confined to the highest-risk quartile of the patient population. An algorithm was developed to classify patients as being at high or low risk for an event based on patient age, New York Heart Association class, history of a prior contrast reaction, and left ventricular end-diastolic pressure. Application of this algorithm for selective use of low-osmolality agents only for high-risk patients to a theoretical population of 1000 patients reduced contrast agent costs 66% without increasing the frequency of contrast agent-related adverse events. The advantages of low-osmolality contrast agents are clinically important in patients with severe heart disease but are not in less ill patients. Universal use of low-osmolality agents for cardiac angiography in an unselected population is not necessary. Appropriately guided selective use of low-osmolality contrast agents is feasible and has the potential to reduce cost substantially without compromising safety or effectiveness.

Clinical Decision Making: Broadening the Responsibilities of Practitioners

To the Editor. —Dr Eddy's 1 article on broadening the responsibilities of practitioners is a stimulating Socratic dialogue between himself and a nominal Kaiser Permanente radiologist, during which the radiologist bravely fights a losing battle trying to defend the use of expensive low osmolar contrast agents (LOCAs). Eddy defends the overall utility of severely limiting the use of LOCAs, even though—because of this decision—40 more patients each year will experience serious, but nonfatal, reactions to less expensive high osmolar contrast agents (HOCAs). This decision saves Kaiser Permanente of Southern California (KPSC) $3.5 million per year, money that will be used to screen more hard-to-reach women for cervical cancer. Eddy argues that such a transfer is of greater benefit to all members of the health maintenance organization. Eddy's conclusion is logically sound when based on the simple binary alternatives provided, but is incorrect if other alternatives are considered. His analysis, for