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Eur Radiol (2002) 12:2807–2812

DOI 10.1007/s00330-002-1630-9 CONTRAST MEDIA

Marie-France Bellin Contrast medium extravasation injury:


Jarl Å. Jakobsen
Isabelle Tomassin guidelines for prevention and management
Henrik S. Thomsen
Sameh K. Morcos
members of the *Contrast Media
Safety Committee of the European
Society of Urogenital Radiology
(ESUR)

Received: 27 June 2002 Abstract Extravasation of contrast Keywords Contrast media ·


Accepted: 8 July 2002 material is a well-recognized com- Extravasation · Risk factors ·
Published online: 6 September 2002 plication of contrast-enhanced im- Prophylaxis · Guidelines · Treatment
© Springer-Verlag 2002 aging studies. The management of
this complication is contentious;
*Members of the Committee: therefore, the Contrast Media Safety
H.S. Thomsen (Chairman, Denmark), Committee of The European Soci-
S.K. Morcos (Secretary, United Kingdom), ety of Urogenital Radiology decided
T. Almén (Sweden), P. Aspelin (Sweden), to review the literature and issue
M.F. Bellin (France), W. Clauss (Schering,
Germany), H. Flaten (Amersham Health, guidelines. A comprehensive litera-
Norway), N. Grenier (France), J.-M. Ideé ture search was carried out. The re-
(Guerbet, France), J.Å. Jakobsen (Norway), sulting report was discussed at the
G.P. Krestin (The Netherlands), F. Stacul 8th European Symposium on Uro-
(Italy), J.A.W. Webb (United Kingdom)
genital Radiology in Genoa, Italy.
Automated power injection may re-
sult in extravasation of large vol-
umes and may or can lead to severe
M.-F. Bellin · I. Tomassin tissue damage. Infants, young chil-
Department of Radiology, dren and unconscious and debilitat-
University Hospital P. Brousse, AP-HP, ed patients are particularly at risk of
University of Paris 11, extravasation during contrast media
14 Avenue Paul Vaillant-Couturier,
94804 Villejuif Cedex, France injection. Fortunately, most extrava-
sations result in minimal swelling
J.Å. Jakobsen or erythema, with no long-term se-
Department of Radiology, Rikshospitalet,
0017 Oslo, Norway quelae; however, severe skin necro-
sis and ulceration may occur. Large
H.S. Thomsen (✉) volumes of high osmolar contrast
Department of Diagnostic Radiology 54E2,
Copenhagen University Hospital at Herlev, media are known to induce signifi-
Herlev Ringvej 75, 2730 Herlev, Denmark cant tissue damage. Compartment
e-mail: heth@herlevhosp.kbhamt.dk syndrome may be seen associated
Tel.: +45-44883212 with extravasation of large volumes.
Fax: +45-44910480
Conservative management is often
S.K. Morcos adequate, but in serious cases the
Department of Diagnostic Imaging, advice of a plastic surgeon is rec-
Northern General Hospital,
Sheffield Teaching Hospitals NHS Trust, ommended. Based on the review
Sheffield S5 7AU, UK simple guidelines for prophylaxis
Contrast Media Safety Committee of the and management of contrast medi-
European Society of Urogenital Radiology um extravasation injuries are pro-
(ESUR) http://www.esur.org/contact.cfm posed.
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Table 1 Simple guidelines for


prevention and management of Risk factors relate to:
extravasation of contrast media The technique
Use of a power injector
Less optimal injection sites including lower limb and small distal veins
Large volume of contrast medium
High osmolar contrast medium
The patient
Unable to communicate
With fragile or damaged veins
With arterial insufficiency
With compromised lymphatic and/or venous drainage
To reduce the risk:
Intravenous technique should always be careful, preferably using plastic catheters for power injection
Use low-osmolar contrast medium
Type of injuries:
Most injuries are minor
Severe injuries include skin ulceration, soft tissue necrosis and compartment syndrome
Treatment:
Conservative management is adequate in most cases
Limb elevation
Apply ice packs
Careful monitoring
If a serious injury is suspected, seek the advice of a surgeon

Introduction management due extravasation injuries. The report was


discussed with the more 300 participants attending the
The European Society of Urogenital Radiology (ESUR) International Symposium on Urogenital Radiology, June
is committed to improving knowledge about contrast 2002, in Genoa, Italy.
media. The Contrast Media Safety Committee of ESUR
has recently produced guidelines for prevention of con-
trast medium nephrotoxicity [1], for the use of intravas- Risk factors
cular contrast media in diabetic patients receiving met-
formin [2] and for the prevention of generalized reac- Patient factors
tions to contrast media [3]. This paper focuses on how to
detect, prevent and treat extravasation injuries due to Infants, small children and unconscious patients are more
contrast media. Their incidence seems to be increasing likely to develop extravasation [4] because they are un-
and there seems to be no consensus among radiologists able to complain of pain at the injection site. Patients re-
regarding treatment. Subcutaneous extravasation is a ceiving chemotherapy are also at a higher risk of extrava-
well-recognized complication of intravenous administra- sation because chemotherapy may induce fragility of the
tion of iodinated and MR contrast media [4, 5, 6, 7]. Its vein wall. Extravasation injuries are more severe in pa-
incidence after mechanical bolus injection is higher than tients with low muscular mass and atrophic subcutaneous
that reported for hand-injection or drip-infusion tech- tissue. In addition, patients with arterial insufficiency
niques, but there seems to be no relation between injec- (e.g. atherosclerosis, diabetes mellitus or connective tis-
tion rate and extravasation frequency [7, 8]. The clinical sue diseases) or compromised venous drainage (e.g.
presentation is highly variable. Most extravasations in- thrombosis) or lymphatic drainage (e.g. radiation therapy,
volve small volumes of contrast material and induce surgery or regional node dissection) are less able to toler-
minimal swelling or localized erythema, which rapidly ate extravasation than those with a normal circulation.
diminish. Extensive tissue necrosis and severe skin and
subcutaneous ulceration are rare and usually follow high
volume extravasations [4, 9]. The Contrast Media Safety Contrast media type and volume
Committee of the European Society of Urogenital Radi-
ology decided to review the literature, prepare a consen- Extravasation of low-osmolar contrast media is better
sus report, and produce guidelines for prophylaxis and tolerated than extravasation of high-osmolar media. The
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osmolality threshold for significant tissue injury is esti- With MR imaging contrast agents, the osmotic loads and
mated to be 1.025–1.420 mOsm/kg water [10, 11, 12, the volumes that are administered are markedly lower
13]; however, four severe injuries have been reported than with iodinated agents; however, in rats extravasa-
with non-ionic contrast media, none of which required tion of dimeglumine gadopentetate (1960 mmol/kg wa-
reconstructive surgery [14, 15, 16, 17]. ter) was associated with a higher incidence of necrosis,
The vast majority of extravasations involve small vol- haemorrhage and oedema than gadoteridol (789 mmol/kg
umes of contrast material and symptoms resolve com- water) [23]; the latter, at a concentration of 0.5 mol/l,
pletely within 24 h [4, 5, 8, 13, 18]. Occasionally, severe was no more toxic than 0.9% saline.
skin ulceration and necrosis can follow extravasation of The second factor is the cytotoxicity of contrast me-
volumes as small as 10 ml [9]. Large-volume extravasa- dia with conflicting results in the literature comparing
tion may lead to severe damage to extravascular tissue ionic and non-ionic contrast. In a laboratory study [24]
and is most likely to occur when contrast medium is in- extravasated ionic contrast media produced acute inflam-
jected with an automated power injector and the injec- mation followed by a chronic inflammatory process,
tion site is not closely monitored [4, 18]. with fibrosis and adjacent muscle atrophy detected at the
injection site by 8 weeks. Early detection is important to
avoid the acute inflammatory response which peaks at
Factors due to injection technique 24–48 h after extravasation [10]. Whereas Cohan et al.
[10] found that ionic contrast media were more toxic
The type of venous access affects the frequency of extra- than non-ionic agents, no difference was found by
vasation. In 40% of one series of patients with contrast Jacobs et al. [8]. The presence of meglumine as a cation
medium extravasation, indwelling intravenous lines were may also play a role in the cytotoxicity of ionic contrast
used [13]. Extravasations are more frequent with metal media [25].
needles than with plastic cannulae [19]. The third factor is the volume of extravasated contrast
The site of injection also appears to be important with medium. Although severe skin lesions have been de-
78% of 36 patients who had contrast medium injected scribed following an extravasation of less than 15 ml, the
through a dorsal vein of the big toe for lower limb ve- majority occurred with large-volume extravasations [26].
nography developing extravasation [19]. The use of tour- The fourth factor is the mechanical compression
niquets and the presence of oedema increase the risk of caused by large-volume extravasations that may lead to
extravasation with lower limb venography [4]. Injections compartment syndromes [14, 15, 16, 17]. Infection of the
into the dorsum of the hand are frequently associated extravasated site may increase the severity of the injury.
with extravasation injury [20]. Extravasation from indwelling intravenous lines is of-
Mechanical power injection for CT studies is respon- ten due to phlebitis which develops in the veins that have
sible for many extravasation injuries. The frequency of been cannulated [4]. Thrombosis increases vascular resis-
extravasation with power injection rates between 1 and tance in the same way as an injection does. Other mecha-
2 ml/s varies from 0.2 to 0.4% [5, 12, 13, 21, 22]. With nisms include the inadequate placement of the catheter in
the development of CT angiography, multiphasic organ the vein, multiple punctures of the same vein, and high
imaging and faster delivery of IV contrast media, it is injection pressure, which can break the vessel wall.
important to assess critically whether extravasation and
reaction rates increase proportionally with injection
rates; however, in a study by Jacobs et al. [8] the extra- Clinical picture
vasation rate (0.6%) did not differ significantly between
groups of patients receiving different injection rates of The presentation of extravasation of the iodinated and MRI
contrast media. In addition, no correlation was noted be- contrast media varies from minor erythema and swelling to
tween the extravasation rate and catheter location, cathe- tissue necrosis associated with progressive oedema and
ter size and catheter type. High-volume extravasation skin ulceration. The injuries may heal or rarely lead to
may occur if the extravasation is deep or if the patient re- long-term sequelae including hypoesthesia, marked weak-
mains asymptomatic. ness and pain [5]. Symptoms of extravasation are very
variable. Many patients complain of stinging or burning
pain, whereas others do not experience any discomfort and
Mechanisms and toxicity remain asymptomatic. On physical examination, the extra-
vasation site appears swollen, red and tender. Most extra-
Multiple factors are involved in the pathogenesis of ex- vasation injuries resolve spontaneously in 2–4 days. At the
travasation injuries. The first factor is osmolality above initial examination it is not possible to predict whether the
1.025–1.420 mOsm/kg water. Both iodinated radiograph- extravasation injury will resolve or will result in ulceration,
ic and MR contrast agents of low osmolality are better necrosis and soft tissue damage. Numerous clinical find-
tolerated than high-osmolar iodinated contrast agents. ings suggest severe injury and justify the advice of a sur-
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geon. These include skin blistering, altered tissue perfu- soconstriction and limits inflammation. The immediate
sion, paresthesia and increasing or persistent pain after 4 h application of warm compresses reduced the volume of
[4]. Extravasation may also result in acute compartmental extravasated fluid in healthy volunteers [35]. In an ex-
syndromes producing tense and dusky forearms, with perimental study application of cold was associated with
swelling and diminished arterial pulses. Compartmental a decrease in the size of skin ulcers produced by extrava-
syndromes may necessitate emergency fasciotomy to re- sation of iothalamate and diatrizoate [11]. In untreated
lieve neurovascular compromise [14, 15, 16, 17]. rats, rats treated with warmth and rats treated with cool-
Extravasation injuries must be distinguished from ing no significant difference was found at the injection
other local reactions to injected fluid including hypersen- site [32]. In humans, cooling can be produced with ice
sitivity reactions and local irritative effects of iodinated packs placed at the injection site for 15–60 min three
contrast agents on the vessel wall. In these reactions times a day for 1–3 days or until symptoms resolve.
oedema and erythema are absent and the catheter is well
positioned in the vein. Transient, local pain has been re-
ported in 2–5% of patients following intravenous admin- Prevention of secondary infection
istration of ionic contrast material, whereas delayed arm
pain at or above the injection site has been reported in Applications of silver sulfadiazine ointment are recom-
0.1–14.0% of patients who received iodinated contrast mended by many plastic surgeons whenever blistering is
material [27, 28]. Pain may last for several days (mean evident [36].
3 days, range 1–30 days) and may progress to phlebitis
in rare cases [29]. Similar features may also be observ-
ed with extravasation of high-osmolar contrast agents. Hyaluronidase and dimethylsulfoxide
Extravasated gadolinium is better tolerated than conven-
tional ionic radiographic contrast media and produces a Hyaluronidase is an enzyme that breaks down connective
zone of signal void on short relaxation time MR images tissue and facilitates absorption of extravasated drugs into
because of its high local concentration [30]. the vascular and lymphatic systems. Local subcutaneous
The presence of a trained nurse or physician beside the injection of hyaluronidase has been in patients with large
patient during contrast medium injection would be ideal extravasation of high- or low-osmolality contrast medium
for early detection, but exposure to ionizing radiation and of chemotherapeutic agents [37]. It should be admin-
makes such close observation impossible. New devices for istered within 1 h of extravasation to obtain quick dissi-
detection of extravasation are currently under evaluation. pation of the skin swelling; doses recommended in the lit-
In a study [31] of 500 patients extravasation detection ac- erature range from 15 to 250 U diluted in 1.5–6 ml of flu-
cessory (EDA) had a sensitivity of 100% and a specificity id [4, 5, 38]. It is well tolerated, with the only known side
of 98% of clinically relevant extravasation (>10 ml). The effect being urticaria. Conflicting results have been pub-
device was easy to use, safe and accurate in the monitor- lished about its efficacy. Most animal and clinical studies
ing of intravenous injections for extravasation, and could suggest a beneficial effect [4, 36, 37], whereas McAlister
prove especially useful in high-flow-rate CT applications. and Palmer [24] reported a deleterious effect.
Dimethylsulfoxide (DMSO) is a free-radical scaven-
ger and an effective solvent. It may also have antibacteri-
Treatment al, anti-inflammatory and vasodilatory properties [39,
40]. It is effective in preventing ulcerations caused by
There is no consensus regarding the best approach for extravasated doxorubicin, but its efficacy has not been
the management of extravasation [4, 5, 32, 33, 34]. The proven for treating extravasation of contrast media.
approaches mentioned below are the ones which have Corticosteroids, vasodilators and a variety of other
been used. agents have been proposed for treating extravasation, but
most studies have failed to demonstrate any value of
these agents or have not evaluated extravasation of con-
Elevation of the affected limb trast media.

Elevation is often useful to reduce oedema by decreasing


the hydrostatic pressure in capillaries. Surgery

Most plastic surgeons believe that the majority of extra-


Topical application of heat or cold vasation injuries heal without surgery and recommend a
conservative policy [12]. Surgical drainage or emergency
Heat produces vasodilatation and thus resorption of ex- suction applied within 6 hours can be effective [41] and
travasated fluid and oedema, whereas cold produces va- the use of emergency suction alone or combined with sa-
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line flushing have also been helpful [20, 42]; however, Conclusion
the efficacy of surgery has not been examined in a ran-
domized trial with conservative treatment as comparator. Extravasation of contrast material is a not infrequent
complication of enhanced imaging studies and large
Aspiration of fluid from extravasated site volume extravasation may result in severe damage.
Early identification is important and conservative
Aspiration of fluid from the injection site is controver- management is effective in most cases. Simple guide-
sial, as it usually removes only a small amount of lines are proposed for prevention and management
extravasated fluid and carries a risk of infection. (Table 1).

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