Key words
CT - contrast agents - extravasation
Introduction
Intravenous application of extracellular contrast media to perform CT and MRI examinations
currently has significant relevance to many clinical issues [1].
A residual risk of extravasation persists despite preventive measures used in radiological
clinical routine, such as the administration of an intravenous test bolus prior to
high-pressure injection of contrast medium [2]. Studies by Lewis and Hecker [3] demonstrated two types of extravasation mechanisms. On the one hand, fluid can escape
into the surrounding tissue through an extraluminally dislocated or perforated catheter
tip; on the other hand, it can leak through the puncture site of an intraluminally
correctly placed the catheter.
The proper medical procedure after detection of extravasation is often difficult to
assess, since extent and consequences at first sight can be varied and misleading.
This uncertainty has led to the publication of various therapy suggestions and action
algorithms [4]
[5]
[6]
[7]
[8]
[9]
[10] which usually identify retrospectively-determined thresholds indicating a particularly
high risk of serious damage and legitimizing an invasive procedure. Many of the therapy
suggestions in the context of contrast agent extravasation mentioned in the literature
have been extrapolated from generalized extravasation therapy, which is based primarily
on the procedure for extravasation after the administration of chemotherapeutic agents
or electrolyte solutions.
In the review of all procedures and techniques, it is striking that the identified
thresholds and recommendations for action have often been adopted regardless of the
chemical properties of various contrast agents and in particular, invasive therapy
concepts were never compared with conservative procedures in randomized control studies.
Furthermore, related therapy recommendations are based partly on publications dating
from before 1990, when automatic pressure injections were not the standard, and non-ionic,
low-osmolar contrast media were not routinely employed.
Contrast media extravasation in radiology
Contrast media extravasation in radiology
Particularly at risk are patients with an inadequate response to pain. High-risk patients
also include persons with atrophic, subcutaneous adipose tissue, limited peripheral
vascular status or pathological lymphatic situation, as well as patients after current
or ongoing chemotherapy with resulting fragile vascular status and clinically difficult
to assess skin color [11]. The incidence of extravasation with the use of iodine-based contrast media varies
in the literature, and is higher for mechanical bolus injection when compared to manual
administration. Thus the data in the literature ranges from 0.1 % to 0.9 % [12]
[13]
[14]. The changeover to automatic pressure injection, among other things, is mentioned
as the reason for a higher incidence. In addition, higher injection rates are cited
as a reason, even though there are studies that could not prove a connection between
the injection rate and extravasation [15]. Of approximately 350 000 contrast medium injections for CT examinations, 451 resulted
in extravasation [16]. The extravasation rate was 0.13 %; among women it was 0.15 %, somewhat higher than
for men, at 0.11 %. Severe complications occurred in only a single case. In general,
depending on the location, toxicity of the administered agent, volume, osmolarity
and state of charge (ionic versus non-ionic), extravasation can lead to negligible
or even serious complications [17]. Clinical symptoms can range from mild erythema to soft tissue necrosis ([Fig. 1]), compartment syndrome [18] or ischemia of an extremity [19]. There are very few articles in the literature describing extravasation complications
during MRI examinations. This may be due to the significantly slower injection rate
and reduced volumes with low osmolarity used for MRI [6]. Nevertheless, extravasation of gadopentate dimeglumine (Gd-DTPA) can result in
edema, necrosis or hemorrhaging [20]. According to Shaqdan et al. the incidence of extravasation during MRI was 0.06 %
(90 cases after 150 000 injections). None of the documented events resulted in severe
complications [16].
Fig. 1 Necrosis on the dorsum of the foot, 16 days after 100 cc extravasation of iopromid
300 mg J/ml via an intravenous access at the dorsum of the foot with a power injector
during a trauma CT scan without any special conservative treatment afterwards (48-year-old
female obese ventilated patient).
In addition to volume and cytotoxicity, osmolarity is considered an essential component
with respect to pathological changes related to extravasation. Contrast media between
290 – 860 mOsm/kg H2O are considered low osmolar; media between 1200 to 2400 mOsm/kg H2O are high osmolar [21]. There is a known direct relationship between osmolarity and cellular lysis. Due
to the somewhat serious side effects of ionic, hyperosmolar contrast media, at present
non-ionic, low-osmolar contrast agents are primarily used in routine radiological
diagnostics [11]
[22].
In the following, conservative therapeutic measures will be presented and discussed
in the context of the literature. The most important invasive procedures mentioned
in the literature in connection with contrast medium extravasation are described and
discussed critically. The aim is to evaluate these methods in terms of their relevance
in accordance with currently used contrast media and technical standards.
Conservative therapeutic approaches to treating contrast medium extravasation
Conservative therapeutic approaches to treating contrast medium extravasation
There are few meaningful scientific studies on conservative non-invasive therapeutic
procedures to treat contrast medium extravasation. However since all the procedures
described below contribute to alleviating pain and possibly preventing possible further
deterioration in general in the sense of “good clinical practice”, we generally recommend
their use in routine treatment of extravasation.
In addition to documentation, the following conservative measures [4] should be employed immediately after extravasation has been determined:
-
Aspiration attempt while the catheter is still in place [23] then removal
-
Raising of the affected limb (if possible above heart level) to reduce edema by reducing
hydrostatic capillary pressure [7]
-
Moderate cooling in the region of the extravasation.
The literature discuses both the application of cold as well as heat. Whereas active
warming theoretically results in vasodilation and resorption of the leaked medium,
and thus to a reduction of associated edema, active cooling provides an anti-inflammatory
effect via subsequent vasoconstriction [24]. At our clinic, the application of a heparin ointment dressing with cooling and
thus consecutive analgesic effect has established itself as a method that is well
accepted by patients. The ointment dressings are applied only to areas where the dermis
is intact. Topical application is contraindicated in cases of fragile skin conditions
and potential ulceration. We should note that in the course of preparing this paper,
we also could not find any evidence for the traditional application of heparin or
other topical methods [25]; nonetheless, the topical use of non-steroidal anti-inflammatory drugs with regard
to analgesic and anti-inflammatory action with significant risk reduction of systemic
side effects has been well researched [26]
[27]. In their guidelines, Bellin et al. recommend the application of cold compresses
in the area of the injection site for 15 to 60 minutes three times a day for up to
three days or until symptoms are no longer evident [4].
There should be an immediate initial assessment with a clinical examination and monitoring
of sensitivity, blood flow and any blistering or ulcerations as well as increased
swelling. We recommend consultation with a (plastic) surgeon as needed in the event
of circulatory or sensory disturbances or skin necrosis, blisters or ulcerations.
In cases of unremarkable blood flow and sensitivity, clinical monitoring should be
performed after one and four hours if necessary.
Splinting and immobilization are especially recommended at constricted areas such
as wrists and ankles. In this case, the splints should be applied to include the adjoining
joint (e. g. in the event of critical extravasation on the back of the hand, a palmar
splint including the wrist and fingers). There are no meaningful scientific publications
regarding the use of splints for contrast medium extravasation. This approach is recommended
despite the absence of supporting medical literature, since the use of splints in
surgery of the extremities corresponds to the clinically accepted standard of basic
care for unstable wounds and infections, regardless of their formation (infected wounds,
wound healing disorder, phlebitis, etc.); furthermore, use of splints also achieves
some pain relief.
Finally, it should be mentioned – as in any medical complication – patients should
be adequately informed regarding further procedure and potential risks in the case
of contrast medium extravasation. In particular, patients should be made aware that
if the symptoms worsen, they should go directly in the radiology department or the
emergency department of the hospital.
Invasive therapy for contrast medium extravasation
Invasive therapy for contrast medium extravasation
Hyaluronic acid injection
The literature describes administration of hyaluronidase via the point at which the
contrast medium has exuded into the surrounding tissue. There is no consensus regarding
dosage, the data range from five to 250 units [11]. Injection of hyaluronic acid into the extravasated area is based on the following
pathomechanism: As a mucopolysaccharide, hyaluronic acid essentially determines the
structure of interstitial connective tissue. Hyaluronidase enzymatically cleaves this
structure and contributes to the distribution of the extravasate, thus promoting its
absorption into the vascular and lymphatic system [28]. The enzymatic effect takes place within minutes and is time-limited.
In this context, the following articles have been primarily cited: In 1998, Federle
et al. [12] retrospectively studied the frequency and effect of ionic, high-osmolar, and low-ionic,
non-osmolar contrast agent extravasation, demonstrating that there is no relationship
between injection rate and frequency or quantity of the leaked contrast agent, and
that the extravasation rate using power injectors increases when compared to manual
injection. The study expressed doubts about the effectiveness of hyaluronidase therapy,
since even high-volume patients without this treatment did not require surgical intervention.
The 1996 article by Cohan et al., [11] also frequently cited in connection with contrast agent extravasates and hyaluronidase,
provides a review of the detection, prevention and status of treatment options for
contrast medium extravasation. However, this work cites many references which include
the extravasation treatment of other agents. The authors conclude that the situations
cited are anecdotal case studies without case control and that hyaluronidase therapy
is not a routine intervention.
In a 1984 animal study of extravasation in which no contrast medium extravasation
was examined, the authors only express the hypothetical conclusion that the positive
effect of hyaluronidase according to the mechanism of action is to be expected for
other agents [28]. In contrast, animal studies by McAlister et al. [29] in 1971 evaluated the immediate and subsequent histological effects of various ionic
high osmolar contrast agents on the subcutaneous and intramuscular tissues which always
show an acute inflammatory response with secondary muscle atrophy and scar formation
after eight weeks. It was demonstrated that application of 25 units of hyaluronidase
into the extravasate actually increased the inflammatory response with consequent
coagulation and scarring. In their study, Vandeweyer at al. describe eleven cases
of extravasation treated with irrigation and aspiration without the use of hyaluronidase,
and mention hyaluronidase only as a conservative treatment option [30].
In summary, the data do not provide any evidence for the use of hyaluronidase as a
therapy for contrast medium extravasation. The literature contains anecdotal case
studies involving contrast agents no longer in use. In our view, this therapeutic
approach should be used as an emergency concept in the sense of off-label use such
as in the case of inoperable patients and contrast medium-associated compartment syndrome.
Aspiration and irrigation
A further therapeutic approach is local dilution followed by aspiration, called wash-out,
aspiration and suction in the literature [30]. Stab incisions are made around the affected area under local or general anesthesia,
and the extravasate is aspirated with blunt suction cannulas. Subsequently the undermined
tissue region is irrigated. Information about the required number of stab incisions
or the volume and type of irrigation solution varies. This procedure should be performed
within a time window of six hours after the extravasation event.
A 1993 article by Gault et al. [19] is frequently cited regarding this procedure in relation to contrast media. This
retrospective study describes 96 extravasation patients, 44 of whom were successfully
treated with irrigation and suction. However, since only one patient with contrast
agent-associated extravasation was included in this population, the effectiveness
of this treatment remains open with respect to radiological practice.
Loth et al. [31] retrospectively describe five cases of extravasation of ionic high-osmolar contrast
media without providing exact data regarding the volume. Surgical drainage and irrigation
was described as successful using several liters of Ringer’s lactate in four of the
five cases, which is explained by the observation of a therapeutic time window of
six hours after the extravasation occurrence.
Vandeweyer at al. [30] describe eleven cases of extravasation between 20 and 90 ml of an ionic, high-osmolar
contrast medium solution and which could be successfully treated within the first
two hours after the event by suction and irrigation. The clinical presentation is
described by the authors with local pain without circulatory or sensory disturbances,
and in two of the eleven cases with blistering.
In summary, the few anecdotal publications regarding this approach only present extravasation
therapies for no longer used highly osmolar contrast media with volumes greater than
20 ml. We currently see an indication for this apparently mechanistically plausible,
but not evidence-based and relatively invasive surgical procedure in the treatment
of drug-based, cytotoxic extravasation, but less so in the treatment of non-ionic
low-molecular contrast agent extravasation.
Manual squeezing technique
Less widespread, but described as effective and easy to perform, is the so-called
manual squeezing technique in which the extravasate is manually expressed after various
punctures or stab incisions.
In 2007 Tsai et al. [32] described their positive experiences with this technique in a retrospective study
over the course of three months in which there were 8 extravasations between 50 – 80 ml
leading to noticeable vascular impairment in the form of cold and numbness. In seven
cases nonionic, low osmolar contrast medium was employed, in one case ionic, high-osmolar
contrast had been used. The catheter was immediately removed, the affected area disinfected,
five to eight punctures generated with an 18 gauge needle, and the fluid manually
expressed. All eight cases healed satisfactorily.
In 2016 Kim et al. [5] published an account of 23 patients with contrast medium extravasation who reported
severe pressure on the limb or cases in which the extravasation volume was greater
than 50 ml. The squeezing technique was applied to all 23 patients, with extravasation
volumes ranging from 5 to 140 ml. After catheter removal, five to ten stab incisions
of three millimeters in length were placed around the access point after disinfection.
This squeezing maneuver was carried out until the extravasate leak dried up. Apart
from temporary, mild epidermolysis and blistering, all cases healed without consequences
within a week. A control group was not described in this study.
In summary, no adequate evaluation of the squeezing technique is possible due to the
very limited available data. From our point of view, the decisive advantage appears
to be the possibility to perform this procedure immediately after occurrence of extravasation
before diffuse contrast medium imbibition of the tissue takes place.
Fasciotomy and compartment release
Fasciotomy is part of the standard repertoire of surgical emergency interventions,
therefore this technique need not be explained here. Pathophysiologically, it is known
that subcutaneous edema can cause skin necrosis, but can also lead to compartment
syndrome due to the increase in intracompartmental pressure [33]. Likewise, the vicious circle underlying edema and ischemia has been described in
the literature [34]. Highly osmolar or toxic agents cause edema which puts pressure on compartments
thus triggering tissue ischemia. The latter, in combination with venous congestion
and low arterial gradients, increases the formation of edema by capillary leakage
and finally leads to necrosis, whereby the risk of necrosis is disproportionately
high in relation to the time sequence.
The literature contains various case reports on the development of compartment syndrome
after contrast agent extravasation [35]
[36]. Fallscheer et al. [37] described the largest series in 2007 in which a group of seven patients were studied
retrospectively. After the application of hyperosmolar, non-ionic contrast medium
extravasation had occurred and which, according to practice of that hospital, was
treated by means of fasciotomy and compartment release. The quantity of extravasate
in the patient cohort who did not receive surgery is not described in the study. Significant
swelling associated with paresthesia or circulatory disturbance or swelling combined
with painful active flexion and passive extension of the affected muscle groups is
considered an indication for surgical intervention. Intraoperatively, subcutaneous
edema was the primary concern, with the time between detection and surgery ranging
from 90 to 300 minutes. All extremities could be preserved. Postoperative complications
described by the authors were temporary movement restrictions, residual lymphoedema
and chronic regional pain syndrome (CRPS type 1). The authors report that after switching
to new, safer power injectors in conjunction with a standardized test injection of
20 ml saline, there was no reduction in the number of extravasations, but events were
recorded faster, and conservative therapy procedures could be initiated, making surgical
treatment unnecessary.
Summary
Considering the aforementioned invasive therapy procedures for contrast medium extravasation,
it is striking that in general these case studies are largely retrospective, entail
a series of small numbers of cases without conservative control groups, some of which
originate far in the past which are no longer comparable with contrast agents currently
in use. On the other hand, there are current reports on the successful management
of extravasation.
In their 2010 retrospective study, Sbitany et al. [38] questioned the need for involvement of a plastic surgeon for contrast medium extravasation
greater than 30 ml. According to their series of 102 patients, each of whom healed
free of complications without surgery, the authors conclude that due to generalized
changeover to non-ionic agents, severe complications no longer arise [21]
[39]
[40]. Likewise, greater extravasation volumes of up to 150 ml can be conservatively treated
without consequence [41]. However, it would be incorrect to conclude that restoration to the patient’s original
condition can be presumed. Contrast medium extravasation continues to be a serious
complication which should be treated according to definite recommendations.
The personnel involved should be aware of the related risk factors. In individual
cases, depending on the radiological problem, for at-risk patients it should be considered
whether the planned examination would allow a lower contrast flow rate. In addition,
catheters that fail to inject a test bolus or permit aspiration, or where the surrounding
tissue is indurated and/or reddened, as well as assesses to small or peripheral vessels
of the lower extremities should not be used.
In the case of extravasation, careful documentation of the following parameters is
obligatory in order to be able to recognize deteriorations in findings at an early
stage and respond adequately: type of contrast agent, amount of extravasation, time
of examination, location of access, and, if possible, sensitivity of affected extremity,
blood flow and status of peripheral pulses ([Fig. 2]). Furthermore, information about skin status, possible epidermiolysis and blistering
or erythema should be provided. If skin changes are present, we recommend marking
the extent and, if possible, photographic documentation and size determination at
a clearly defined location (anatomical fixed points). Documentation should be stored
in the HIS (Hospital Information System) or in the patient file, if possible, in order
to be accessible to all practitioners.
Fig. 2 Suggestion for documentation of extravasation for contrast media. The document can
be downloaded at https://www.drg.de/de-DE/4338/kontrastmittel-paravasate/.
In summary, we agree with Sbitany et al. [38] in recommending consultation with a plastic surgeon in the event of extravasation
volumes greater than approx. 150 ml. Exceptions are cases in which there is a visible
impairment of the soft tissues, sensory or circulatory disorders independent of the
amount of extravasate; in such cases inclusion of a plastic surgeon should take place
as an emergency measure. An algorithm of our recommendations for extravasation, which
was developed under the patronage of the German Society of Plastic, Reconstructive
and Aesthetic Surgeons (DGPRÄC) ([Fig. 3]), can be downloaded from the Internet as a DIN A4 printout at https://www.drg.de/de-DE/4338/kontrastmittel-paravasate/.
Fig. 3 Flow-Chart for radiological contrast media extravasation. The flow-chart was prepared
in collaboration with the DGPRÄC (German Society for Plastic, Reconstructive and Aesthetic
Surgery) and can be downloaded at https://www.drg.de/de-DE/4338/kontrastmittel-paravasate/.
Thanks to modern technology and innovations in pharmacology, the risk of serious consequences
after contrast media extravasation has fortunately been significantly reduced [37]
[38]. However, the occurrence of extravasation is not declining, only the incidence of
consequential damage, meaning that severe complications in the form of tissue necrosis
and compartment syndrome can still occur even after extravasation in small volumes
[41]
[42]. Since there are no clear risk criteria for the development of complications with
serious consequences, and since these cases are rarities, it is important to remain
vigilant with all contrast medium extravasations and to regularly check the incidence
in your own department in order to eliminate possible sources of risk.
