Torsten Almén

Contrast medium extravasation injury: guidelines for prevention and management.

Abstract. Extravasation of contrast material is a well-recognized complication of contrast-enhanced imaging studies. The management of this complication is contentious; therefore, the Contrast Media Safety Committee of The European Society of Urogenital Radiology decided to review the literature and issue guidelines. A comprehensive literature search was carried out. The resulting report was discussed at the 8th European Symposium on Urogenital Radiology in Genoa, Italy. Automated power injection may result in extravasation of large volumes and may or can lead to severe tissue damage. Infants, young children and unconscious and debilitated patients are particularly at risk of extravasation during contrast media injection. Fortunately, most extravasations result in minimal swelling or erythema, with no long-term sequelae; however, severe skin necrosis and ulceration may occur. Large volumes of high osmolar contrast media are known to induce significant tissue damage. Compartment syndrome may be seen associated with extravasation of large volumes. Conservative management is often adequate, but in serious cases the advice of a plastic surgeon is recommended. Based on the review simple guidelines for prophylaxis and management of contrast medium extravasation injuries are proposed.

Contrast-Medium-Induced Nephropathy Correlated to the Ratio Between Dose in Gram Iodine and Estimated GFR in ml/min

Purpose: To suggest a more precise tool when assessing the risk of contrast-medium-induced nephropathy (CIN), i.e. the ratio between contrast medium (CM) dose expressed in grams of iodine (g-I) and estimated glomerular filtration rate in ml/min (eGFR; based on equations using serum-creatinine (s-Cr), weight, height, age, and/or sex), here named I-dose/GFR ratio. Material and Methods: A Medline search of published CIN investigations reporting mean eGFR and mean dose of low-osmolality CM (LOCM) identified 10 randomized controlled prophylactic and 2 cohort coronary investigations, and 3 randomized and 1 cohort computed tomographic (CT) investigation. From the randomized trials, data were collected only from the placebo or control arms, unless there was no significant difference between the control and test groups. The mean I-dose/GFR ratio of each study was correlated with the mean frequency of CIN-1 (s-Cr rise⩾44.2 µmol/l or ⩾20–25%) and CIN-2 (oliguria or requiring dialysis). A maximum dose according to an I-dose/GFR ratio = 1 in patients with s-Cr ranging from 100 to 300 µmol/l was compared with that of Cigarroas formula and with a “European consensus” threshold published by the European Society of Urogenital Radiology, both using s-Cr alone to predict renal function. McCulloughs formula was used to assess the risk of CIN requiring dialysis at an I-dose/GFR ratio = 1 with LOCM. Results: The coronary investigations revealed a linear correlation with a correlation coefficient between the I-dose/GFR ratio and the frequency of CIN-1 and CIN-2 of 0.91 (P<0.001) and 0.84 (P = 0.001), respectively. At a mean I-dose/GFR ratio = 1, the regression line indicated a 10% risk of CIN-1 and a 1% risk of CIN-2. At a mean I-dose/GFR ratio = 3, the risk of CIN-1 and CIN-2 increased to about 50% and 15%, respectively. Pooled weighted data from the CT investigations revealed a 12% risk of CIN-1 at a mean I-dose/GFR ratio = 1.1 and no cases of CIN-2. The maximum CM dose according to an I-dose/GFR ratio = 1 was about 30–50% of that of both Cigarroas formula and the “European consensus” in elderly low-weight individuals, while it was similar for middle-aged individuals weighing about 90 kg. McCulloughs formula suggests that there will be an exponentially increasing risk of CIN requiring dialysis, but at an I-dose/GFR ratio = 1 and using LOCM it will not exceed 1% until GFR decreases below 30 ml/min in diabetics and below 20 ml/min in non-diabetics. Conclusion: Using the I-dose/GFR ratio may be a more expedient way of improving risk assessment of CIN than todays common practice of estimating CM dose from volume alone and renal function from s-Cr alone. Prospective studies based on individual patient data are encouraged to define the risk of CIN at various I-dose/GFR ratios and correlated to type of CM, examination, risk factors, etc.

Serial phlebography of the normal lower leg during muscular contraction and relaxation

It has long been known that compression of the veins by the muscles is an important factor in assisting the return of blood to the heart, and particularly the return of blood from the lower leg and the foot (LE DENTU 1868, BRAUNE 1889, Mc PHEETERS et coll. 1932, BARCROFT & DORNHORST 1948, BARCROFT & SWAN 1953). Our notions of the actual mechanism by which muscular contraction brings about this effect are however still vague. The wide use of phlebography in the investigation of circulatory diseases of the leg increases the necessity of detailed knowledge of the flow characteristics of the blood in the normal leg in diagnostic radiology. It was in an attempt to fill this gap that the present investigation was started ; the results are described below. Material and methods. The material consisted of 13 apparently healthy volunteers (3 males and 10 females) aged 22 to 70. Three subjects were examined bilaterally. With the subject sitting, the lower leg vertical and the foot resting flat on a support before a cut film changer, 40 ml Urografin 60 yo were injected into a dorsal vein (injection time 15 to 60 sec) of the relaxed foot. Just before conclusion of the injection the film changer was started, and a few seconds later the patient was instructed to raise and lower the heel alternately with maximum

Contrast Media-Induced Nephrotoxicity: Survey and Present State

Reports of renal failure induced by contrast media are increasing. Adverse effects of contrast media on kidney function include diuresis, changes in renal blood flow, osmotic nephroses, albuminuria, enzymuria and, most important, glomerular filtration rate. Animal studies indicate that the new nonionic contrast medium, iohexol, has fewer adverse effects on kidney function than the ionic media currently used. Three clinical studies offer some evidence of the effect of iohexol on renal function, but it is not yet possible to conclude that lower nephrotoxicity found in animals will also be found in man. Further clinical studies are warranted, and careful monitoring of contrast media clearance is recommended in all high-risk patients.

Determining 'true' glomerular filtration rate in healthy adults using infusion of inulin and comparing it with values obtained using other clearance techniques or prediction equations.

Objective. To determine ‘true’ glomerular filtration rate (GFR) in healthy adults as renal clearance following infusion of inulin, and compare that result with those obtained using other markers and clearance techniques and with estimations of GFR using creatinine-based prediction equations. Material and methods. Twenty healthy volunteers (11 females) with a median age of 27 years (range 19–36 years) received bolus doses of inulin and iohexol i.v. and 16 blood samples were taken after injection. Then, inulin and iohexol were infused to give stable plasma concentrations and blood and urine samples were collected. Residual bladder volume was estimated using ultrasound scanning. Plasma and urine concentrations of inulin and iohexol were determined using chromatography and resorcinol methods, respectively. Different methods of GFR determination were compared as well as four formulae for GFR estimation based on serum creatinine. Results. ‘True’ GFR, i.e. renal clearance of inulin during its infusion, was a median of 117 ml/min/1.73 m2 (inter-quartile range 106–129 ml/min/1.73 m2). Similar values of GFR were obtained with renal clearance of iohexol during its infusion and also with plasma (body) clearance of inulin or iohexol following bolus injections and using 16 or five plasma samples. Endogenous creatinine clearance was higher (p<0.001) than true GFR (median 23 ml/min/1.73 m2). Plasma clearance of iohexol and inulin based on their concentrations in four blood samples underestimated their renal clearance considerably. All four creatinine-based formulae markedly underestimated renal inulin clearance. Conclusions. Plasma and renal clearance of iohexol and inulin were similar in healthy adults. Underestimation of GFR was noted when plasma clearance of iohexol and inulin was based on four but not five or more blood samples. Some prediction equations underestimate true GFR to such an extent that caution must be taken when using them to evaluate normal or high GFR values.

Noninvasive Estimation of Kidney Function by X-ray Fluorescence Analysis: Elimination Rate and Clearance of Contrast Media Injected for Urography in Man

A noninvasive method for the estimation of kidney function is described. The use of radioactive tracers and the sampling of plasma and urine are omitted. The method has been used in patients referred for urography and who had therefore been injected with routine amounts of iodine-containing urographic contrast medium. After urography, the elimination rates of urographic contrast medium from both serum and finger tissue were determined and compared during a 2-hour period that began two hours after injection of contrast medium. The elimination of iodine in finger tissue was measured noninvasively using x-ray fluorescence analysis. A strong degree of correlation was found between the elimination rates from serum and finger tissue and between the total clearances calculated from the serum and finger measurements. Thus, after urography estimation of kidney function may be obtained as a fringe benefit by x-ray fluorescence measurements of the elimination rate of an iodine-containing contrast medium from tissue or from serum.

Development of nonionic contrast media.

In this brief history, the author reviews the observations that led to his developing a nonionic contrast medium. Current knowledge suggested that if a water-soluble medium could be made isotonic to human plasma, it would cause less pain and toxicity than the ionic media then in use. The principles and design of such a medium are discussed, as well as the subsequent chemical development and testing in animal models of first generation (metrizamide) and second generation (iohexol) nonionic media. Iohexol, which is described as a nonionic, monomeric ratio 3 contrast medium, was selected for clinical testing from among competing substances due to its low toxicity in a number of animal models. The results from these experimental models predicted that iohexol would cause fewer and less severe adverse reactions in clinical use than ionic ratio 1.5 media.

Contrast media: the relation of chemical structure, animal toxicity and adverse clinical effects.

Chemotoxicity and osmotoxicity of contrast media (CM) are determined by chemical structure. The lower the chemotoxicity and osmotoxicity of the CM, the less animal toxicity and higher clinical tolerance in humans will be achieved. Nonionic monomers such as iohexol and iopamidol in iodine-equivalent concentrations have approximately half the osmolality and therefore half the osmotoxicity of ionic monomers such as diatrizoate, iodamide, iothalamate and metrizoate. Absence of carboxyl groups in nonionic CM, as opposed to the presence of carboxyl groups in ionic CM, results in a lower chemotoxicity in nonionic CM. Similarly, a larger number of hydroxyl groups in nonionic CM than in ionic CM result in a lower chemotoxicity. The lower chemotoxicity of nonionic CM is reflected as a higher subarachnoid and intravenous tolerance both in animals and in the clinical setting.

Are intravenous injections of contrast media really less nephrotoxic than intra-arterial injections?

AbstractWe oppose the opinion that the intra-arterial administration of iodine-based contrast media (CM) appears to pose a greater risk of contrast medium-induced nephropathy (CIN) than intravenous administration since 1) in intra-arterial coronary procedures and most other intra-arterial angiographic examinations, CM injections are also intravenous relative to the kidneys, 2) there is a lack of comparative trials studying the risk of CIN between intra-arterial and intravenous procedures with matched risk factors and CM doses, 3) a bias selection of patients with fewer risk factors may explain the seemingly lower rate of CIN after CT in comparison with coronary interventions, 4) the rate of CIN following intra-arterial coronary procedures may also be exaggerated owing to other causes of acute kidney failure, such as haemodynamic instability and microembolisation, 5) roughly the same gram-iodine/GFR ratio (≈1:1) as a limit of relatively safe CM doses has preliminarily been found for both intravenous CT and intra-arterial coronary procedures and 6) the substantially higher injected intravenous CM dose rate during CT relative to an intra-arterial coronary procedure might actually pose a higher risk of CIN following CT. Key Points • Most intra-arterial injections of contrast media are intravenous relative to the kidneys.• No evidence that intravenous CM injections should be less nephrotoxic than intra-arterial.• Considerably higher dose rates of CM are used for CT relative to intra-arterial procedures.• Higher dose rates may pose higher nephrotoxic risk for intravenous based CT studies.

Proteinuria following nephroangiography. I. Clinical experiences.

Following nephroangiography with an ionic contrast medium (metrizoate) proteinuria occurred in 25 of 28 patients, reaching its maximum with 1/2 to 24 hours. It fell to preangiographic values within 6 days. The degree of proteinuria varied but was massive, i.e. more than 10 g albumin/g creatinine, in 9 patients. The underlying mechanism is a marked, reversible increase in glomerular permeability.