Ionic Low-osmolar Contrast Media Research Articles

Early Encephalic Toxicity after Inadvertent Intrathecal Injection of Low Osmolar Contrast Medium

Only nonionic contrast media are allowed for intrathecal use because of their lower neurotoxicity. In case of inadvertent intrathecal administration of an ionic contrast medium, the typical following syndrome is called ascending tonic clonic seizure syndrome. We describe the case of a 61-year-old woman with low back pain who underwent myelography. Ioxaglate, a water-soluble ionic low osmolar contrast medium was accidentally injected intrathecally. She first presented encephalic signs of neurotoxicity, followed by opisthotonic spasms and respiratory distress. In our case, ioxaglate is a low osmolar agent, leading to early encephalic toxicity (preceding medullary signs), because of its cephalic migration. The patient was successfully treated by sedation, anticonvulsant therapy and fluid hydration. Intrathecal administration of an ionic contrast medium is clearly contraindicated. In case of inadvertent injection of a low osmolar product, encephalic signs are seen first.

Impact of anticoagulation on ionic and nonionic contrast media effect on thrombogenesis and fibrinolysis: The PEPCIT study

The effect of ionic low osmolar contrast media (ICM) and nonionic iso-osmolar CM (NICM) on acute thrombotic complications of percutaneous coronary intervention (PCI) is subject to controversies possibly related to a potential interaction with anticoagulation regimens. We sought to compare physical and morphological properties of fibrin clots made in the presence of ioxaglate (ICM), iodixanol (NICM) versus control and to evaluate the effect of four anticoagulants used in PCI. Maximum platelet aggregation (MPA%), maximum elastic modulus (EM, dyne/cm(2) ) fiber density (n/10(-5) /μm(2) ), and lysis front velocity (nm/sec) of fibrin rich clot (FRC) were measured simultaneously using peripheral blood from 12 patients undergoing elective PCI. We compared the effects of adding iodixanol or ioxaglate or saline (control) to blood with enoxaparin, unfractionated heparin, fondaparinux, and bivalirudin. Iodixanol and ioxaglate led to nonsignificant reduction in MPA compared to control (33.6% ± 16.9%, 28.2% ± 18.9%, and 40.7% ± 13.9%, respectively, P = ns). Fibrin formed with iodixanol was stiffer (42.7 ± 41.9, 18.7 ± 3.7, and 15.9 ± 9 dyne/cm(2) , P < 0.01) and displayed more fibrin fibers (1089 ± 175, 260 ± 108, and 456 ± 131 n/10(-5) /μm(2) , respectively, P < 0.01) than with ioxaglate or control. This resulted in a profound reduction in the lysis front velocity (191 ± 95, 261 ± 112, and 360 ± 153 nm/sec). None of the four anticoagulants displayed any significant interaction on the effect of contrast media. The prothrombogenic effect of iodixanol is related primarily to an increase in fibrin stiffness with subsequent delayed fibrinolysis, something not seen with ioxaglate. Anticoagulation does not appear to have any impact on this fibrin clot abnormalities.

Ionic Low-Osmolar Versus Nonionic Iso-Osmolar Contrast Media to Obviate Worsening Nephropathy After Angioplasty in Chronic Renal Failure Patients: The ICON (Ionic versus non-ionic Contrast to Obviate worsening Nephropathy after angioplasty in chronic renal failure patients) Study

This randomized, prospective, double-blind, multicenter study compared nephrotoxicity of the nonionic iso-osmolar contrast media (CM) iodixanol versus the ionic low-osmolar CM ioxaglate in patients with chronic renal insufficiency undergoing coronary angiography. The properties of iodinated CM might contribute to the incidence of contrast-induced nephropathy (CIN). Patients with renal impairment undergoing coronary angiography were randomly assigned to iodixanol (n = 72) or ioxaglate (n = 74). Baseline characteristics were well-matched between the 2 groups. The predicted risk score for CIN was similar in the iodixanol and in the ioxaglate groups (11.9 +/- 4.1 vs. 11.8 +/- 4.1), as was the use of N-acetylcysteine (70% vs. 73%). The primary end point of the study, median peak increase of serum creatinine from day 0 through day 3 after angiography, did not differ between the iodixanol (0.09 mg/dl; interquartile range 0.00 to 0.30 mg/dl) and the ioxaglate (0.15 mg/dl; interquartile range 0.00 to 0.40 mg/dl; p = 0.07) groups. The percentages of patients with a peak increase of serum creatinine >or=0.5 mg/dl (15.9% in iodixanol vs. 18.2% in ioxaglate), >or=1.0 mg/dl (1.4% vs. 4.5%), and >or=25% or >or=0.5 mg/dl (15.9% vs. 24.2%, respectively) also did not differ significantly between the 2 groups. In high-risk patients undergoing coronary angiographic procedures, use of the nonionic iso-osmolar CM iodixanol does not reduce renal deterioration in patients with renal impairment, compared with the ionic low-osmolar CM ioxaglate. Given that the study was underpowered to compare nephrotoxicity of the 2 groups under the active medical protection of CIN, a larger randomized study is warranted that will enroll patients with higher risks of CIN under a strict control of hydration regimens and adjunctive medications.

Economic analysis of the use of contrast media during percutaneous coronary interventions in France and Spain

SummaryThe iso-osmolar contrast medium iodixanol (Visipaque™; GE Healthcare, UK) has been reported to reduce the risk of major adverse cardiac events and to have a higher success rate when used during percutaneous coronary intervention (PCI) compared with the ionic low-osmolar contrast medium ioxaglate (Hexabrix; Guerbet, France) for patients at risk of complications. This study assessed to what extent these clinical benefits translate into economic benefits for patients undergoing PCI in France and Spain using a decision tree model. Clinical data were derived from the COURT and VIP trials. Medical resource use data were obtained from panels of French and Spanish interventional cardiologists. Resource use was converted to costs using country-specific tariffs. The study results suggest that using iodixanol rather than ioxaglate confers an economic benefit in addition to the reported clinical benefit in high-risk patients undergoing PCI in both countries. For low-risk patients, iodixanol may be regarded as cost-effective when relating the extra cost to the small reported increase in angiographic success.

Thrombotic risk associated with the use of iodinated contrast media in interventional cardiology: pathophysiology and clinical aspects

A review of the current knowledge of the anti-thrombotic properties of iodinated contrast media (CM) has been conducted. CM are classified according to their chemical structure, either ionic or non-ionic (monomeric or dimeric). Numerous in vitro and in vivo data show that, although all CM have anti-coagulant properties, ionic molecules are more potent than non-ionic and, furthermore, do not activate resting platelets, unlike non-ionic agents. These properties may lead to a decrease in thrombus formation during interventional procedures. Several clinical trials have shown that CM may play a role in the occurrence of acute thrombotic complications but also in delayed ischaemic events during interventional procedures. A recent meta-analysis showed that, compared to non-ionic monomers, ionic low-osmolar CM reduce the rate of coronary artery abrupt closure, but no significant difference was found with respect to ischaemic complications. Ionic CM lead to a lower deposit of thrombotic materials on catheters and guide-wires. To date, clinical data comparing ionic CM and non-ionic dimers are scarce, significantly heterogeneous and, unlike experimental data, they do not show differences between both classes of CM. Further studies are required to better understand the precise mechanisms of such interactions and to analyse the effect of CM when new antiplatelet agents or new procedures (stenting) are used, to comply with new clinical strategies.

A randomized trial of low osmolar ionic versus nonionic contrast media in patients with myocardial infarction or unstable angina undergoing percutaneous transluminal coronary angioplasty

Objectives. The purpose of this study was to determine prospectively whether the differences in anticoagulant and antiplatelet effects of ionic and nonionic contrast media alter angiographic or clinical outcomes in patients with unstable ischemic syndromes undergoing percutaneous transluminal coronary angioplasty.Background. The interaction of platelets and thrombin with the endothelium of injured vessels contributes to thrombosis and restenosis after coronary angioplasty. Case reports and retrospective observations have reported an increased risk of thrombosis with the use of nonionic contrast media.Methods. A total of 211 patients with acute myocardial infarction or unstable angina undergoing coronary angioplasty were randomized to receive nonionic or ionic low osmolar contrast media. Coronary angiograms were assessed by a technician blinded to the study contrast media, and clinical events were monitored by an independent nurse for 1 month.Results. Patients receiving the ionic media were significantly less likely to experience decreased blood flow during the procedure (8.1% vs. 17.8%, p = 0.04). After the angioplasty, residual stenosis, vessel patency, the incidence of moderate to large thrombi and use of adjunctive thrombolytic therapy were similar between the two groups. However, patients receiving ionic media had fewer recurrent ischemic events requiring repeat catheterization (3.0% vs. 11.4%, p = 0.02) and repeat angioplasty during the initial hospital stay (1.0% vs. 5.8%, p = 0.06). One month after angioplasty, patients receiving ionic contrast media reported significantly fewer symptoms of any angina (8.5 vs. 20.0%, p = 0.04) or of angina at rest (1.4% vs. 11.8%, p = 0.01) and a reduced need for subsequent bypass surgery (0% vs. 5.9%, p = 0.04), compared with patients receiving the nonionic media.Conclusions. These findings demonstrate that in patients with unstable ischemic syndromes undergoing coronary angioplasty, the use of ionic low osmolar contrast media reduces the risk of ischemic complications acutely and at 1 mouth after the procedure. Therefore, low osmolar ionic contrast media should be strongly certified when performing interventions in patients with unstable angina or myocardial infarction.

Diagnostic efficacy and safety of two low-osmolar contrast media in cerebral angiography

A comparative randomised open study was carried out in 120 patients uncle undergoing cerebral angiography, to compare two low-osmolar contrast media (LOCM). All the patients participated voluntarily in the trial. Half the patients (n = 60) received sodium and meglumine ioxaglate (Hexabrix 320) and the other half (n = 60) iohexol (Omnipaque 300). Contrast agent efficacy was evaluated at the different cerebral levels explored. Adverse reactions were recorded immediately and 24 h post-administration. Diagnostic quality was considered excellent in 95% of cases with Omnipaque and in 97% of cases with Hexabrix. Image quality was excellent in 95%, of cases with Omnipaque and in 100 % of cases with Hexabrix. In terms of both efficacy and safety, no significant difference was observed between the agents. Thus, low osmolality would appear to be the essential factor in this indication as far as safety is concerned. No significant difference in safety was noted between the ionic LOCM Hexabrix and the non-ionic LOCM Omnipaque.

Profound platelet degranulation is an important side effect of some types of contrast media used in interventional cardiology.

Thrombotic complications occurring during coronary angiography and percutaneous transluminal coronary angioplasty (PTCA) are relatively frequent and can be influenced by the type of radiographic contrast media used. Low osmolar contrast media (LOCM), both ionic and nonionic, have been considered to be safer than the older high osmolar contrast media (HOCM), causing less haemodynamic and symptomatic side effects. Recently, however, nonionic LOCM have been associated with an increased incidence of thrombotic events, including coronary occlusion and stroke. The effects of commonly used contrast media on platelets in native blood were investigated using immunolabeling and flow cytometry to detect platelet activation in vitro. A nonionic LOCM (Omnipaque) caused profound platelet degranulation in nearly 80% of platelets compared with 2 to 3% of platelets in the control. Conversely, an ionic HOCM (Urografin) caused only 25% degranulation, whereas an ionic LOCM (Hexabrix) caused no platelet activation and, furthermore, it inhibited the effects of thrombin on platelets. Platelet degranulation, quantified by immunolabeling, was paralleled by release of beta-thromboglobulin and platelet factor 4 from platelet alpha-granules. Blood from patients anticoagulated with heparin and pretreated with standard-dose aspirin in preparation for PTCA showed the same pattern of contrast media-induced platelet activation as normal subjects. These results suggest that the type of contrast media used during invasive imaging of the vasculature could have a significant effect on platelets. Platelet degranulation within a PTCA-damaged vessel would be increased by a nonionic contrast medium, releasing procoagulant molecules and platelet-derived growth factors into the damaged vessel lumen, which might contribute to acute thrombosis and the initiation of the restenosis process.

Risk of thrombosis during coronary angioplasty with low osmolality contrast media

Studies in vitro have suggested that nonionic low osmolar contrast agents produce an increase in thrombogenicity. To determine the incidence of thrombi related to the use of nonionic low osmolar contrast media during coronary angioplasty, a double-blind randomized study was performed in 100 patients. Medication before angioplasty included oral aspirin (250 mg/day) in all cases. At the beginning of the procedure, aspirin (250 mg) and heparin (10,000 U) were intravenously administered. During the procedure patients were randomly assigned to receive either an ionic low osmolar contrast agent ioxaglate (n = 50), or a nonionic low osmolar contrast media iohexol (n = 50). The presence of thrombus was evaluated on the angiogram and on the guidewire immediately after its retrieval from the patients. Clinical, angiographic and procedural variables were similar in the 2 randomized groups. Angiographic evidence of thrombus was observed in 1 patient (2%) assigned to ioxaglate and in 11 patients (22%) assigned to iohexol (p < 0.005). One patient (2%) from the ioxaglate group and 6 patients (12%) from the iohexol group showed thrombotic residues on the guidewire (p = not significant). Three patients had acute myocardial infarction, 1 patient (2%) receiving ioxaglate and 2 patients (4%) iohexol (p = not significant). There were no deaths. Thus, compared with an ionic low osmolar contrast media ioxaglate, the nonionic low osmolar contrast agent iohexol increases the incidence of thrombus during coronary angioplasty.

The Effects of Ioxaglate 320, Iohexol 350, and Iopamidol 370 on Erythrocyte Aggregation

The authors report a randomized, double-blind prospective trial comparing the effects of nonionic with ionic low-osmolar contrast media on erythrocyte aggregation. The study group comprised 40 consecutive patients with pathology necessitating selective angiography. Patients were examined using either ioxaglate 320, iohexol 350, or iopamidol 370. Erythrocyte aggregation was assessed both macroscopically and microscopically. Erythrocyte aggregation occurred more frequently in the iopamidol group (13 of 45 samples examined) than in the iohexol (4 of 46) or ioxaglate (5 of 51) groups (P = .002).

Variable Effects of Radiological Contrast Media on Thrombus Growth in a Rabbit Jugular Vein Thrombosis Model

We studied the effect of an ionic high osmolar contrast medium (Ioxitalamate), an ionic low osmolar contrast medium (Ioxaglate) and various nonionic low osmolar contrast media (Iopamidol, Iopromide and Iohexol) on thrombus growth in a rabbit jugular vein thrombosis model. Thrombus growth was determined by the accretion of 125I-labeled fibrinogen onto autologous preformed thrombi in rabbit jugular veins at various time-intervals from 15 min up to 10 h after infusion of the study solution. The ionic low osmolar contrast medium markedly inhibited thrombus growth whereas all nonionic low osmolar contrast media promoted thrombus growth. The ionic high osmolar, contrast medium inhibited thrombus growth, but less than the ionic low osmolar contrast medium. Within the group of nonionic contrast media, the Iopamidol associated promotion of thrombus growth was significantly higher than the Iopromide or Iohexol associated effects. The simultaneous administration of the apparently most potent thrombus growth promoting contrast medium (i.e. Iopamidol) and heparin resulted in complete abolishment of the increase in thrombus growth. These results support the claims of prothrombotic properties of nonionic as compared to ionic contrast media and could explain the clinically encountered thromboembolic complications after the use of nonionic low osmolar contrast media.

Effect on Thrombus Growth and Thrombolysis of Two Types of Low Osmolar Contrast Media in Rabbits

Thromboembolic complications have been reported after diagnostic or interventional radiological procedures. However, contrast media inhibit platelet function and blood coagulation in vitro. To investigate these characteristics in vivo, we determined the effect of nonionic and ionic low osmolar contrast media on thrombus growth and thrombolysis in rabbits in a randomized study design. Rabbits received either ionic low osmolar contrast medium (ioxaglate), nonionic low osmolar contrast medium (iohexol) or saline. Thrombus growth was determined by the accretion of 125I-labeled fibrinogen on to autologous, nonradioactive, preformed thrombi in rabbit jugular veins. Thrombolysis was assessed by measurement of the decrease in radioactivity of standard sized preformed 125I-fibrinogen labeled thrombi. Ioxaglate significantly inhibited thrombus growth (60% inhibition, P less than 0.005 vs. saline), in contrast to iohexol, which had no significant effect (33% inhibition, P less than 0.2 vs. saline). Neither ioxaglate nor iohexol affected thrombolysis.

Pervenous Hepatic Transplant Angiography Using a New Low Osmolar Contrast Medium An Experimental Study in Dogs

The patency of the vascular anastomoses in a canine liver transplantation model was imaged by serial pervenous angiography using ioxaglate, which is a new ionic low osmolar contrast medium. No premedication or general anesthesia was administered. No major adverse reaction was noted, not even after repeated angiography. Except for the occurrence of one hematoma formation and one paravenous injection, which resolved without leaving sequellae, no local complications occurred. Sufficient information regarding the patency of the hepatic artery anastomosis was obtained in 94% of the angiographic studies, while in 70% the patency of the caval anastomoses could be determined. In addition, portal vein patency was imaged in 21% of the angiograms. Even better visualization results can be expected when combining this method with video subtraction techniques, although patient cooperation or general anesthesia would then be mandatory.