Complications of Radiographic Contrast Material

Learning Objectives: After reading this article, the physician should be able to:

1. Discuss the incidence and risk factors of soft tissue extravasation of IV contrast material.

2. List the criteria for diagnosing soft tissue extravasation of IV contrast material.

3. Identify the complications of and recommend treatment for soft tissue extravasation of IV contrast material.

Emergency physicians are often called on to order numerous studies that entail the use of intravenous contrast material. We are all aware of the occasional anaphylactoid reactions that occur, a nightmare for the radiology department, the patient, and the ordering physician. There are, however, other clinical considerations surrounding the use of contrast materials, including the effect on renal function, and the inadvertent extravasation of the dye into the soft tissues.

It is not uncommon to get a call from radiology saying they are sending over a patient (always a bad way to start a conversation) who had IV infiltrate during a dye injection. The arm is now swollen with up to 100 mls of contrast material that never made it to the venous system. This usually means a repeat study for the patient, and a few anxious moments while the gravity of the situation is pondered. The EP must then consider what to do. Radiologists are the true experts in this field, and they often handle the episode totally. Most minor extravasations never make it to the ED. The burden of evaluating and treating an aliquot of such a patient often ends up in the ED's mix of the sick and injured.

Fortunately, the advent and now routine use of newer and less toxic contrast agents has markedly reduced serious reactions, including anaphylactoid reactions. Local tissue reactions, once a formidable problem, have all but disappeared. Although the newer contrast agents are hugely more expensive than their predecessors, most radiology departments have changed their protocols to use the newer and less toxic agents exclusively.

This month's column begins a series of discussions on contrast material and the actions and reactions that are relevant to the emergency physician. The first discussion will focus on the extravasation of contrast material into the soft tissues.

Extravasation of Radiographic Contrast Material: Recognition, Prevention and Treatment, Cohan R, et al, Radiology, 1996;200(3):593

This self-proclaimed state-of-the-art presentation in a radiology journal presents an extensive and complete discussion of the issue of extravasation of radiographic contrast material. It's about all you will have to read on this subject. This excellent and erudite article is essentially a review of the frequency and mechanisms of extravasation and the resultant injuries from the dye, complete with a focused discussion of a variety of recommended treatment alternatives.

Frequency of Extravasation: Fortunately only a small number of patients experience a significant extravasation or any significant morbidity when intravenous contrast material errantly makes its way into most soft tissues. Extravasation of chemotherapeutic agents is a much more significant problem, occurring in 0.1 percent to 0.7 percent of patients receiving chemotherapy. About 10 percent of children admitted to the hospital have an extravasation episode, usually of benign intravenous fluids. The frequency of dye extravasations varies with the type of diagnostic study. It occurs most frequently during lower extremity venography, a study that is currently a lost art. This is probably because such venography injections are performed into edematous extremities, often while a tourniquet is still applied. In addition, very small veins are cannulated for this study, such as a vein in the dorsum of the great toe. It is well known that the highest incidence of extravasation occurs when a metal needle, such as a butterfly used for venograms, is used to penetrate the vein and infuse the material. Teflon catheters inserted in the same location have a much lower incidence of extravasation.

Figure. Its easy to ...

With the increasing use of CT scans, the number of reported dye extravasations has markedly increased over the past 10 years. This is often attributed to the fact that there is widespread use of a dynamic bolus technique, using automated programmed injectors to deliver the dye. The technician no longer stands at the bedside injecting the contrast material with a syringe. Techs are usually behind the lead shield and merely press a button to automatically and quickly inject the dye into the vein. The injection is often specifically timed to coincide with a radiographic image. The reported frequency of extravasation during CT scan is still under one percent even when mechanized rapid bolus infusion techniques are employed. However, when rapid bolus injection techniques are used, significant volumes of contrast material may be involved. The automatic pumps deliver the material at a fixed flow rate and pressure even if the catheter has been dislodged from the vein. It would not be uncommon to see a 20 to 50 ml extravasation or more with the newer techniques for helical CT scanning.

More severe soft tissue injuries from extravasated dye have occurred with the use of the older non-diluted ionic contrast materials, dyes that are rarely used these days. These older substances have a very high osmolality, sometimes up to 1400 mOsm/kg. Ulceration, necrosis, and chemical cellulitis are the end result of soft tissue injection of these contrast materials. The more common nonionic contrast materials are much less toxic when they end up in the subcutaneous tissue.

Fortunately, significant extravasation reactions from dyes used in radiographic studies are much less common than the disasters seen with extravasation of vasopressors, hypertonic glucose, calcium, hyperalimentation solutions, or chemotherapies. Well known chemotherapy culprits are doxorubicin, vincristine, and adriamycin. Severe skin necrosis has been noted with these agents, and extravasation can result in long-term morbidity, including continuing sensory disturbances, contractures, residual stiffness and pain, and decreased range of motion if a joint is involved. Skin grafting may be required if the infiltrated solution is particularly toxic.

Those patients at risk for contrast material extravasation often can be prospectively identified. The authors note that infants, the elderly, and unconscious patients, or someone who is otherwise unable to complain about pain at the injection site are more likely candidates for extravasation. The more peripheral the vein, the more likely the extravasation. The dorsum of the hand is a common initial IV site, but also a more common site for extravasation.

Radiologists usually require a more central site for today's CT scanning techniques, and the antecubital fossa is the currently preferred site. If an old or prior indwelling intravenous line is used for dye injection, the incidence of extravasation also increases. If an IV site is covered with a large amount of gauze or tape, early extravasation may go undetected. Occasionally extravasation can occur through a previously unsuccessful cannulation site when the dye is injected in the same vein either proximally or distally.

The extent of injury after extravasation also is dependent on individual patient characteristics. Those with arterial insufficiency, compromised vascular or lymphatic drainage, diabetics, and patients with soft tissue diseases fare less well after extravasation. The elderly and the very young also do not tolerate dye in their subcutaneous tissue as well as a healthy teenager or adult. The dorsum of the hand and foot are prime candidates for morbidity from extravasation into this less forgiving thin tissue. The antecubital fossa is the site of least morbidity secondary to extravasation.

Figure. Extravasatio...

Mechanism: If an IV has been in place for sometime and phlebitis has developed, extravasation is more likely, even if the tip of the catheter is still well positioned in the vein. Over time, indwelling catheters tend to produce a larger hole in the vein, lending themselves to extravasation from even a properly placed catheter. Phlebitis is usually not a problem in the first 24 hours of a properly placed IV catheter, but the incidence increases dramatically over time if the vein has been used for other injections. Phlebitis theoretically slows the infusion rate and increases back pressure, forcing dye out of the vein's original puncture site.

Table. Risk Factors ...

Extravasation of previously used ionic contrast media is a significant insult to the skin and subcutaneous tissue, with a peak inflammatory response noted at 24 to 48 hours. An acute inflammation is followed by a more chronic inflammatory response, including fibrosis, muscle atrophy, and other pathologic changes that may not peak until four to eight weeks. Therefore, maximum damage from these agents may not be appreciated for up to 48 hours following extravasation. Nonionic dyes, the ones consistently now used, do not create such characteristic problems. The precise mechanism of dye toxicity is not known, but it is largely attributed to hyperosmolality and mechanical compression from large volumes.

The Effect of the Specific Contrast Media: The extravasation of low osmolality contrast material is well tolerated, producing miniscule problems compared with the older high osmolality ionic contrast media. Most of the currently used low osmolality agents produce similar minimal toxicity, although there is some variation in toxicity of the older agents that is product specific. The nonionic agents produce a less overall inflammatory action, probably because they have a significant lower osmolality. They are consistently better tolerated.

Even large volumes of extravasated nonionic contrast material (up to 150 ml) seem to be well tolerated in most patients. The majority of extravasations, even large ones, resolve spontaneously and do not produce lasting injury to the skin or subcutaneous tissue. In fact, the authors of this 1996 study state that their review of the literature found only three reports of severe injuries produced by the extravasation of nonionic contrast material. One report included skin ulceration after a 150 ml antecubital extravasation in an unconscious patient undergoing an injection for a CT scan. In this case, a blood pressure cuff located proximal to the vein was inadvertently inflated during the injection.

In another patient, an acute compartment syndrome was diagnosed, likely secondary to the 180 ml volume of dye administered by a power injection into the forearm. This patient required a fasciotomy. In another patient, a 60 ml extravasation in the dorsa of the hand resulted in swelling and blistering at the injection site and a compartment syndrome. Importantly, none produced skin ulcerations or necrosis severe enough to require skin grafting or plastic surgery, although a fasciotomy is a significant intervention.

Clinical Presenation: Many patients do not experience severe discomfort during an extravasation of the newer contrast dyes. They may be relatively asymptomatic, even with large volume extravasations. At the site of extravasation, the skin is usually swollen and red, with varying degrees of tenderness. Findings are directly proportional to the volume of the extravasation. Minor discomfort may last for two to three days although most patients feel better or back to normal within a few hours. The initial examination is unable to predict the eventual outcome so a period of observation is prudent. In two to four hours, however, the clinician should know if there is going to be a problem. Increasing local findings and worsening symptoms should be considered a harbinger of a more serious ultimate outcome.

Treatment: The authors state that there have been very few laboratory studies that have specifically investigated the treatment of the extravascular injection of contrast media. Most of the literature has concentrated on chemotherapeutic agents and other more toxic intravenous solutions. Animal studies have formed the basis of most of our current knowledge. Various interventions for the treatment of a variety of fluid extravasations have yielded a marked variation in conclusions and recommendations.

It is probably impossible to aspirate a significant amount of contrast material from subcutaneous tissue. Although some authors have made an attempt to aspirate fluid via the same needle through which the extravasation occurred, this is likely a useless endeavor. Elevation of the effected extremity is generally suggested as initial therapy, but the true value of this intervention is unknown. There is no consensus on the use of the topical applications of heat or cold. Animal studies on all interventions give conflicting results.

There seems to be some credence for the use of immediate topical cooling, but this intervention is unlikely to have a major effect on outcome. If topical blistering does occur, it's generally treated like a burn, usually with the use of silver sulfadiazine (Silvadene). The use of dilution techniques to diminish the concentration of the extravasated agent has been postulated to be a benefit, but this intervention has not been proven to be of any clinical value. With the nonionic contrast agents, this is likely of no benefit. The authors of this paper did not advocate any attempts to dilute the concentration of extravasated dye. The obvious problem is that additional fluid volume can cause additional trauma and elevate tissue pressures, enough to potentially precipitate a compartment syndrome.

A number of local antidotes have been suggested to ameliorate the injury caused by extravasated agents. Most of this work has been done with chemotherapeutic agents. The two agents that have been suggested are hyaluronidase and DMSO. Hyaluronidase is an enzyme that breaks down hyaluronic acid, the mucopolysaccharide responsible for connective tissue structure. Breaking this down is believed to permit the spread of extravasated substances over a larger area, thereby reducing the local toxicity. Experimentally it appears to work within a few minutes of injection, and it is most beneficial if given within one hour of the extravasation.

Figure. The antecubi...

Although this agent is thought to be useful for chemotherapeutic extravasation, it has no known benefit for preventing contrast material sequelae. Likewise, the use of DMSO, corticosteroids, and vasodilators (such as phentolamine) have no proven benefit for extravasation of contrast material. While surgical treatment of an extravasated injury may be effective for chemotherapeutic agents, it has no place in the treatment of extravagated contrast material injuries. A fasciotomy may occasionally be required to treat the rare compartment syndrome secondary to contrast dyes, but this should be an extremely unusual occurrence. Interestingly, liposuction has been suggested as a treatment for severe extravasation of highly toxic materials. All in all, prevention and extra care in the high-risk patient are certainly the best ways to prevent extravasation and its sequelae.

Reccommendations: The authors recommend that policies and procedures be in place to help prevent or minimize extravasation of contrast material. Such policies include close observation of the injection, the routine use of nonionic contrast material, and a careful selection of the IV injection site. If an extravasation occurs, they recommend elevating the extremity and placing an ice pack for approximately 20 to 30 minutes. The recommendation is to keep the patient in the radiology suite for two to four hours to follow the patient's course, with consultation and follow-up as needed. If there is any indication of excessive pressure, progressive signs or symptoms, ulcerations, blistering, or a large volume infiltration, they suggest referring immediately to a plastic surgeon. The volume of nonionic contrast material that is considered potentially problematic is greater than 50 to 100 ml, depending on the site. They believe that outpatient follow-up is quite appropriate for the vast majority of cases, and certainly for those who experience no significant adverse or progressive problems in two to four hours. The conclusion is that extravasation of nonionic contrast material, although common, rarely causes any severe injury.

Comment: There are many issues concerning the ED use of contrast material, but fortunately extravasation is the least of our problems. In the old days when we had only high osmolality ionic dyes, with osmolalities reaching 2000 mOsm/kg, the extravasation of even a few cc was often a painful and distressing event. Large extravasation could lead to tissue necrosis, skin grafts, and persistent pain and stiffness, particularly in the elderly and children. The authors of this article present a cogent and extensive review of the extravasation issue, and conclude that essentially it is currently a non-issue with regard to long-term outcome. For the patient undergoing a CT scan, particularly if it's an emergency study from the ED, any breach in protocol or complication is greatly magnified. When you tell a patient that you screwed up his IV injection, he wonders if you also screwed up the diagnosis and treatment, immediately creating a credibility crisis that complicates our already difficult job. It is probably easy to explain away a minor extravasation, but when there is a red and tender milliliter fluid bulge in the forearm, the patient thinks the worst.

This article presents useful information and techniques to minimize extravasation and to identify patients at highest risk. The issue of extravasation is much more complicated when phenytoin, 50% dextrose, colchicine, vasopressors, and calcium solutions are involved because the mechanism and issues with these substances are completely different.

It would not be considered a breach of standard of care to allow a small extravasation to occur. Most of the time, they can't be totally prevented. The incidence of minor extravasation is unknown, but Federle et al (Radiology 1998;206(3):637) concluded that the complication rate is higher if an automatic device injects the dye. When dye was injected with a mechanical bolus injection via a plastic catheter placed in an upper extremity, about one percent of patients experienced an extravasation. Curiously, the injection rate did not influence the extravasation rate. Although 16 patients had a volume of at least 50 mls of dye extravasate, none required surgical intervention and none had long-term effects. Other authors also have concluded that the rate of injection is not correlated with extravasation rates (Radiology 1998;209(2):411).

The non-verbal the patient who can't complain or inform the nurse or tech about the burning IV is probably our biggest issue. The elderly tend not to say anything because they are so afraid of the hospital. Of course, infants and children are unable to voice their displeasure or do so throughout the ED stay no matter what you do. This is largely a radiology-initiated problem because contrast dyes are almost exclusively administered in the radiology suite. EPs are not there to pass along our caveats or concerns, but the prescient clinician can preempt problems and help limit extravasations.

It would be wise to make sure that a free-flowing IV is present, eschew the dorsum of the foot and hand for dye studies, and avoid covering the injection site with a lot of gauze that will hide a potential problem. The nursing staff in the ED should be aware that multiple punctures of the same vein are a set up for extravasation, even if the final site is proximal to the first needle stick. The use of long-term indwelling lines is less of an issue for the ED, and an IV site less than 24 hours old is usually not problematic from a phlebitis standpoint. But inflamed veins do not accept good flow rates. Repeated movement of ED catheters does tend to enlarge the entrance hole over time. I would not use the arm on the same side as a prior mastectomy, and would not inject dye in the arm that has a dialysis graft/shunt unless no suitable alternatives exist.

Our radiology department will not administer IV contrast for a PE CT study unless there is an 18 gauge needle in the antecubital fossa. Current CT PE studies use the automatic injector, and a standard PE study will inject 120 ml of contrast material (such as Optiray 320) at a rate of 4-5 ml per second. Usually the entire injection proceeds without direct visualization by the tech so the entire amount can be quickly administered. The pumps cannot sense a problem and don't stop or alter the infusion rate when the dye does not go where it is supposed to go. Because these dyes are not very irritating, many patients do not even realize that the extravasation is occurring. Even if they were able to voice a concern, the rapidity of the injection probably precludes significant intervention. There are some devices that have tried to teach the injector pump to limit the injection if extravasation is occurring, but I am not certain of their current availability (Amer J Radiol 2000;174(2):315).

Figure. IV dye is al...

I don't think any ED-ordered contrast study would use a butterfly needle. Venograms are almost dinosaurs these days, so the issues surrounding these topics are moot for the ED. I have seen no literature on specific problems or benefits from the use of the external jugular vein or femoral or subclavian veins for dye administration sites. One would intuit that a central line will not infiltrate. We have used implanted IV ports and PICC lines for dye injection. I suppose a temporary dialysis catheter could support IV dye in a pinch.

Our radiologists do not want to use neck/subclavian central lines for helical CT scan PE studies because the dye load from the superior vena cava is not conducive for a good study. There are some other mechanical/logistical problems I cannot understand for other studies. A femoral line is satisfactory for a PE study because the computerized helical CT can make adjustments and coordinate the timing of the dye injection with the x-ray. The site for dye administration for a head or abdominal CT study is not problematic because it does not have the timing issues involved with hunting for a PE. Some protocols and additional caveats are institution-specific.

Although the patient may not realize he had an extravasation, the radio-opaque properties of the dye make detection of the volume and extent of infiltration immediately accessible to a plain radiograph. It is always a bit of a shock to find a large area of white stuff in somebody's arm, but it does go away rather quickly. Within a few hours, much of the extravasated dye has been absorbed into the general circulation. A larger problem is the fact that the study may not have been completed properly, and the issue of repeat injection of nephrotoxic dye comes up.

Aggressive ED procedures are gratifying when successful, and emergency physicians like to intervene whenever they can. However, there is very little one need do - or can or should do - with the extravasation of nonionic contrast material. Non-intervention is usually the best policy. It's simply not much of an issue in the long run, although a large extravasation can produce a few anxious moments when a patient is rushed to the ED. Minor pain and phlebitis may occur a few days later, but we usually don't see such patients because they are handled by the radiology staff. The authors of this study suggest keeping the patient in the radiology suite, but there is little chance of that occurring in most hospitals these days if observation for more than a few minutes is required. Hopefully public relations begins with the technician and radiologist who do not overestimate the severity of the extravasation, unnecessarily upsetting the patient. Rushing a patient to the ED is a bad tactic, especially if he has to wait hours to see the emergency physician after the precipitous transfer.

Although it may seem like a nifty idea to attempt dilution, inject corticosteroids, or manipulate other agents to ameliorate the reaction, these efforts should be put on hold. There is probably no problem using an icepack and evaluation, but it's important to note that no intervention has been found to be particularly helpful. I have seen a number of patients with this problem, even with an entire 120 ml bolus in the arm, and generally a few hours of observation and reassurance is all that is required. This is not the same issue involved with infiltration of levophed, colchicine, dilantin, or chemotherapies. Hyaluronidase is an old antidote for some extravasations, but I don't think it is currently available.

The radiologists in this study seem to think that plastic surgeons will readily respond to a large infiltration. It has been my experience that they tend not to get involved because there is so little to do. Generally any infiltration becomes an ED/radiology issue. It's comforting to know that even large volumes of today's contrast material are essentially benign. However, one needs to be on the lookout for potential compartment syndromes and circumstances where the large volume of fluid is the issue, not particularly the content of the fluid. Certainly residual or increasing pain, blistering, excessive tissue distension, or change in the distal circulation or sensory exam would be cause for concern. Otherwise, a course of benign neglect is the best tactic. I found that taking an x-ray and repeating it in about two hours at the time of discharge demonstrates to the patient that the dye is almost gone and that this is an unfortunate but not significant compilation.

See Bellin et al (Contrast medium extravasation injury: Guidelines for prevention and management. EUR Radiol 2002;12(11):2807) for another more recent and in-depth discussion on this topic.