Judith A. W. Webb

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.

Safety of MR liver specific contrast media

Over the past few years a number of magnetic resonance (MR) liver specific contrast agents have been introduced. In this report the safety issues of these agents are addressed. A literature search was carried out. Based on the available information, simple guidelines on the safety issue of liver specific contrast agents have been produced by the Contrast Media Safety Committee of the European Society of Urogenital Radiology. The report and guidelines were discussed at the 11th European Symposium on Urogenital Radiology in Santiago de Compostela. Liver specific contrast agents appear in general to be safe and well tolerated. However, the incidence of adverse reactions with iron oxides and the intravenous manganese based agent seems to be slightly higher than with gadolinium based agents. However, no safety information from comparative clinical trials has been published. Guidelines on the safety aspects are presented.

Long-term urodynamic effects of finasteride in benign prostatic hyperplasia: a pilot study.

A group of 69 men with bladder outflow obstruction due to benign prostatic hyperplasia (BPH) were treated in a double-blind placebo-controlled study with finasteride (Proscar), a 5 alpha-reductase inhibitor, 5 mg or 10 mg/day, or an identical placebo for 3 months; subsequently, 20 patients received finasteride 5 mg/day in an open extension study. Ten of these patients have now completed 3 years of therapy and have been reevaluated with pressure/flow urodynamics. In finasteride-treated patients dihydrotestosterone (DHT) declined by over 60%, remaining unchanged with placebo. Symptom scores fell in both groups of patients, maximum flow rate values decreased on placebo but improved by a mean of 1.5 ml/s in the 10-mg group and 3.3 ml/s in the 5-mg group. After 1 year of therapy, the reduction in symptom score was well maintained and the flow rate had increased by a mean of 2.7 ml/s; the mean prostate volume was reduced by 14% and prostate-specific antigen (PSA) had declined by 28%. In the 10 patients treated for 3 years who consented to further urodynamic study, the maximum urinary flow rate had improved from a mean baseline value of 8.7 ml/s to a mean of 13.8 ml/s, while maximum subtracted voiding pressure had decreased from a mean baseline value of 72 cm H2O to an unobstructed mean value of 44 cm H2O. Side effects were minimal and reversible on stopping the medication.(ABSTRACT TRUNCATED AT 250 WORDS)

Gadolinium contrast media during pregnancy and lactation

Regulatory approval of new drugs, including subsequent new indications, requires that they have undergone preclinical and clinical testing which focuses on safety and efficacy. For contrast media these tests have never included pregnant and lactating women to investigate possible effects on the fetus and neonate. The summary of product characteristics or the package insert includes a statement about this lack of knowledge. Current practice is not based on formal testing, but on small series and case reports of pregnant and lactating women from the peer-reviewed literature, and on our understanding of the pharmacokinetics of contrast media in pregnant and lactating subjects based on animal data. Although no contrast media have been approved for use in pregnant and lactating women, this does not mean that they are contraindicated, but use of contrast media in these subjects will always be off-label. Before 2006 most radiologists believed that gadoliniumbased contrast media were safe and that they could be used when indicated in pregnant and lactating women. The documentation of a link between nephrogenic systemic fibrosis (NSF) and exposure to some gadolinium-based contrast media changed the situation. Now the most unstable agents (those most likely to release gadolinium) are absolutely contraindicated in pregnant women and in lactating women the milk produced within 24 h of administration must be discarded. The other more stable agents may be used in pregnant women if enhanced magnetic resonance imaging (MRI) is clinically indicated, and lactating women can continue breast feeding after enhanced MRI if they wish. Gadolinium-based contrast media have not shown mutagenic or teratogenic effects in animal experimental studies (1). They can cross the placenta in both directions and although they are water soluble, their molecular weight (500–850 Da) means that relatively small amounts cross the single layer of chorionic epithelium which separates the maternal blood from fetal tissue. Pharmacokinetic studies have used mice and rats because murine and human placentas are structurally similar. The maximum fetal concentration was 0.07% of the injected dose when pregnant mice were given high doses of gadoterate meglumine (0.5 mmol per kg) (2), and the maximum fetal gadolinium concentration was only 0.01% of the injected dose when pregnant rats were given 0.3 mmol per kg of gadodiamide (3). Gadolinium contrast agents in the fetal blood are excreted by the fetal kidneys into the bladder which empties into the amniotic fluid. Reabsorption of amniotic fluid occurs both by fetal swallowing and across membranes into the fetal circulation, from which it can cross the chorionic epithelium back into the mother. The whole amniotic fluid volume turns over every 24 h (4). The half-lives of gadodiamide in mouse fetal tissues and the amniotic fluid were 4 h and 5 h, respectively, after a dose of 0.5 mmol per kg to the pregnant mother, with only tiny amounts of gadolinium detectable in the fetus and none detectable in the amniotic fluid at 48 h (2). Similarly, only traces of gadodiamide were detected in fetal tissue at 24 h when pregnant rats were given gadodiamide 0.3 mmol per kg (3). A total of 57 infants whose mothers were given gadopentetate dimeglumine (0.1–0.2 mmol per kg) showed no adverse effects (5–10). Excretion of gadolinium contrast media into milk is limited because the molecules are water soluble and show minimal protein binding. When 20 lactating women were given 0.1–0.2 mmol per kg of gadopentetate, ,0.04% of the dose given was excreted in the milk over 24 h (11). It was estimated that ,1% of the recommended intravenous dose for an infant reaches the gut after a lactating mother is given gadolinium contrast agents intravenously (11). Doses of 0.1 to 0.2 mmol/kg of gadopentetate and gadodiamide are tolerated intravenously by neonates (12, 13). When gadolinium contrast agents are given orally, only tiny amounts are absorbed – ,1% in a study of gadopentetate (14). Thus only a very small amount of gadolinium contrast media should reach the fetal blood when a lactating woman is given gadolinium contrast agents. In gadolinium contrast media, the gadolinium is bound with a chelating agent to prevent exposure of the body to free gadolinium, which is toxic. The molecules of the nonionic linear gadolinium agents gadodiamide and gadoversetamide are the least stable, so gadolinium is more likely to be released from them. Again, according to laboratory studies, ionic linear chelate molecules (gadopentetate dimeglumine, gadobenate dimeglumine and gadofosveset) have intermediate stability and the macrocyclic agents gadobutrol, gadoteridol, and gadoterate meglumine are the most stable. The stability of gadolinium contrast agents affects the amounts of gadolinium which are retained in the tissues after administration. Tweedle et al. (15) described retention of gadolinium in the liver and bone of mice and rats 14 days after administration of gadolinium agents, with greater amounts retained with linear than macrocyclic agents. Sieber et al. (16) gave high doses of gadolinium agents to rats and found the highest gadolinium concentrations in skin, bone, and liver with gadodiamide. There was 10 times less gadolinium retention in the skin with gadopentetate and 30 times less with gadoterate and gadobutrol. In patients who had received gadolinium agents, four times more gadolinium was retained in the bone after gadodiamide than after gadoteridol (17). The amounts of gadolinium retained in the skin increased over time in patients with NSF (18), raising the suggestion that gadolinium stored in bone might be released over time.

Computed tomography in the follow-up of retroperitoneal fibrosis

Serial abdominal computed tomography (CT) scans have been performed in 15 patients with biopsy-proven idiopathic retroperitoneal fibrosis. Twelve patients had abdominal CT both before diagnosis and at a variable time later. All 12 patients showed a decrease in the size of the retroperitoneal mass at follow-up, although two had not been treated with steroids. The remaining three patients who had abdominal CT at some stage after diagnosis all showed a small residual retroperitoneal mass. Based on the findings, guidelines for the use of CT in the follow-up of retroperitoneal fibrosis are discussed.

Reducing the risk of iodine-based and MRI contrast media administration: Recommendation for a questionnaire at the time of booking

This paper presents a practical questionnaire to be used when a contrast medium examination is requested. The questionnaire is based on the guidelines from the European Society of Urogenital Radiology. Its aim is to identify patients at increased risk of clinically relevant renal and non-renal adverse reactions to iodine-based and MRI contrast agents. The questionnaire should be completed by the referring physician when the examination is requested.

Spiral computed tomography in the diagnosis of renal masses

In conventional CT, the tube and detectors are connected to the power supply by cables. The tube/detector system rotates around the patient in 1±2 s and generates an axial image. The tube then has to return to the initial position to unwind the cables. This takes 6±8 s and is termed the interscan delay, during which the patient is moved to the next table position. The patient suspends respiration for each scan but breathes during the interscan delay. The sequence is repeated until the entire abdomen is imaged, which takes 10 min or longer with some of the older machines. There are several limitations to this technique. Because of the time taken, optimal opaci®cation is not always possible after the intravenous injection of contrast medium. The patient may breathe differently for each scan so that the scans may not be contiguous. Such mis-registration can be a particular problem when trying to detect and characterize small renal lesions. Another major limitation is the partial volume effect. If a lesion is not totally encompassed within the chosen CT slice, incorrect CT attenuation values are obtained because there is averaging between the CT numbers of the lesion and the surrounding kidney. It is particularly important to avoid partial volume averaging when trying to characterize small masses. Accurate CT attenuation values are necessary to identify small amounts of fat in an angiomyolipoma or con®rm that a lesion is a cyst. In spiral CT, slip rings have replaced the cables connecting the tube to the power source [1] allowing the X-ray tube to rotate rapidly and continuously in one direction. High-output X-ray tubes allow continuous radiation production for periods of >70 s. The table moves throughout the period of data acquisition. Instead of individual slices, a volume of data is generated and slices can be reconstructed at any position within the volume. The data are acquired during suspended respiration and the entire kidneys can be imaged in 30 s. The ratio of the speed of the movement of the table (expressed in cm/s) to the thickness of the slice is termed the pitch. Thus with a slice thickness of 1 cm, using a gantry rotation of 1 s, at a pitch of one, the table moves at 1 cm/s. Increasing the pitch to >1 allows a shorter scanning time or, more usefully, it also means that narrower collimation can be used to cover the same distance in the given time, with a consequent increase in spatial resolution, as slice width determines spatial resolution.

The role of imaging in adult acute urinary tract infection

Abstract. Imaging is required in only a minority of patients with urinary tract infection. Some patients who present with severe loin pain are imaged because ureteric colic is suspected. If urinary tract infection does not respond normally to antibiotics, imaging is undertaken to check for evidence of renal obstuction or sepsis. Finally, after the acute infection has been treated, imaging is required in some patients to check for factors pre-disposing to renal damage or to relapsing or recurrent infection. This review discusses the appropriate choice of imaging technique to use in each clinical situation and summarises the expected findings.

Post-contrast acute kidney injury – Part 1: Definition, clinical features, incidence, role of contrast medium and risk factors

PurposeThe Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) has updated its 2011 guidelines on the prevention of post-contrast acute kidney injury (PC-AKI). The results of the literature review and the recommendations based on it, which were used to prepare the new guidelines, are presented in two papers.Areas covered in part 1Topics reviewed include the terminology used, the best way to measure eGFR, the definition of PC-AKI, and the risk factors for PC-AKI, including whether the risk with intravenous and intra-arterial contrast medium differs.Key Points• PC-AKI is the preferred term for renal function deterioration after contrast medium.• PC-AKI has many possible causes.• The risk of AKI caused by intravascular contrast medium has been overstated.• Important patient risk factors for PC-AKI are CKD and dehydration.

The Lalli and Weber effects and the incidence of acute non-renal adverse reactions to contrast media.

Some radiologists have learned that their manner and manifest anxiety render them unsuitable agents for the administration of contrast media. I would recommend that individuals injecting these materials adopt the mien of equanimity urged upon us by Sir William Osler, treat their patients with gentleness and inapparent concern and not arouse their anxieties or increase their fear.” Anthony LF Lalli, 1980 (1)