Chemotherapy Extravasation

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• Intravenous infusion pumps can be particularly dangerous because they can inadvertently force fluid into an extravascu-lar space, producing a compartment syndrome. Pediatric patients can be especially at risk for pump-related problems since the automatic shut off pressure of the pump may be gauged for adult physiology.

• A specific protocol for administration of doxorubicin hydrochloride (Adriamycin) should be followed. Preventable problems have been identified as producing extravasation events, such as failure to release a proximal tourniquet, use of poor veins, or infusion administered under pressure. Small-diameter polyethylene catheters are better than sharp needles, which tend to puncture the posterior vessel wall.

• Application of heat to an extravasation injury is not indicated. It will produce vasodilation, increased interstitial edema, increased swelling, and periarticular stiffness. Use of cool compresses and strict elevation is much better for immediate care.

Differential Diagnosis

Forearm compartment syndrome due to intravenous extravasation Forearm compartment syndrome due to chronic compression Forearm ischemia due to proximal vascular occlusion Forearm muscle necrosis due to sepsis or localized infection


Forearm Compartment Syndrome Due to Intravenous Extravasation

The prognosis for extravasation injuries can be characterized by four key variables: (1) the volume of material extravasated, (2) the type of material that has extravasated, (3) the amount of time that extravasated material has been present (also called the "necrosis interval"), and (4) the susceptibility of the host to injury.

Loth et al (1991) have classified the severity of extravasation into three types (mild, moderate, and severe) based on the amount of extravasated agent. Mild extravasations present with minimal swelling and pain and represent small volume injuries. No blistering or redness is present and the patient can be treated with elevation of the extremity and a compression dressing. Moderate extravasations present with an area of soft tissue inflammation of 10 cm in diameter or less. Significant local tenderness and pain are present, although narcotics pain medication is rarely required. Some erythema may be present but blistering of the skin is absent. Moderate injuries are usually caused by extravasation volumes of 1 to 5 cc. Again, conservative measures such as elevation, cool compresses, and a compression dressing constitute the main form of treatment, although the patient may have residual symptoms for up to a month after injury.

Severe extravasation injuries typically result from large volumes of agent and produce severe pain and local soft tissue changes, such as blistering, erythema, and dramatic swelling. Compartment syndrome may result, which would require immediate fasciotomy. In the absence of compartment syndrome or other vascular compromise, specific management of severe extravasations is influenced heavily by the type of extravasated agent involved.

The type of extravasated agent constitutes the second major variable that influences prognosis for these injuries. Extravasated agents can be grouped into two main categories: vesicants and nonvesicants. Vesicants are materials that can produce local tissue necrosis. Chemotherapy drugs are an example of vesicants, with doxorubicin (Adriamycin) and mitomycin commonly producing dramatic local tissue necrosis. Calcium solutions, potassium solutions, fluorescein, sodium bicarbonate, and radiographic contrast media are also examples of vesicant agents. Some vesicant agents produce tissue necrosis via specific cellular mechanisms, such as inhibition of DNA synthesis, whereas other vesicants, such as electrolyte solutions, produce hyperosmolar states and cause cell death by fluid shifts or dramatic pH changes. Many vesicants are capable of producing a deep level of tissue necrosis that may take days or weeks to demarcate.

Two particular vesicant agents merit special mention. Vasoconstrictor drugs that extravasate can be particularly dangerous, producing either a compartment syndrome or severe local ischemia and tissue death. Local injection of phentolamine may reverse ischemia and prevent disaster. Ultimately, surgical drainage may be required if ischemia cannot be reversed within 3 to 6 hours. Radiographic contrast is another common vesicant agent that can produce local tissue death. Obtaining a radiograph of the involved extremity can be helpful in delineating how much tissue is affected. In cases where more than 20 cc of contrast is involved, surgical decompression is usually indicated; postdrainage radiographs should be obtained to confirm satisfactory removal of the contrast material.

Nonvesicant agents do not typically produce local tissue necrosis but do have the potential to cause significant inflammation; these agents are also sometimes called "irritants." Examples of nonvesicant agents include blood products, Valium, methotrexate, and albumin. Most nonvesicant extravasations can be treated non-operatively as long as circulation is not compromised and large volumes of agent are not involved.

The necrosis interval has been described as the time between the moment of injury and the point at which irreversible tissue death occurs. Surgical drainage performed during this time interval can dramatically improve outcome, because the toxic agent will be removed before tissue necrosis has occurred. The necrosis for many chemotherapy drugs is 72 hours, whereas the necrosis interval for vasoconstricting drugs and radiographic contrast media can be as short as 4 to 6 hours. For those situations in which the patients first present after the necrosis interval has passed, surgical debridement is often better delayed. This is because nothing is gained by immediate debridement (because irreversible necrosis has already occurred) and the area of dead tissue often takes days or even weeks to clearly demarcate.

Figures 26—1, 26—2, and 26—3 illustrate treatment algorithms for managing extravasation injuries due to chemotherapy agents, radiographic contrast materials, and vasoconstrictive drugs, respectively.

Radiographic Contrast Media
Figure 26—1. Treatment algorithm for chemotherapy agent extravasations. (With permission from Loth TS, Eversmann WW. Extravasation injuries in the upper extremity. Clin Orthop 1991;272:248-254.)
Figure 26—2. Treatment algorithm for radiographic contrast material extravasations. (With permission from Loth TS, Eversmann WW. Extravasation injuries in the upper extremity. Clin Orthop 1991;272:248-254.)
Figure 26-3. Treatment algorithm for vasoconstrictive agent extravasations. (With permission from Loth TS, Eversmann WW Extravasation injuries in the upper extremity. Clin Orthop 1991;272:248-254.)

Host factors also influence the prognosis of extravasation injuries. Advanced age, immune compromise, nutritional deficits, steroid dependency, and preexisting peripheral vascular disease are all common host factors that can greatly amplify the damage caused by any given extravasation event.

Remember that the mainstay of conservative management is elevation, use of a cool compress, and a loosely wrapped splint to protect and rest the injured part. Although it may seem obvious, make sure that the offending intravenous catheter is removed so that no more agent can extravasate, and make sure that the affected extremity is not further compromised by tight circumferential items such as jewelry, hospital identification bracelets, or tight bandages. Application of heat to the affected area often makes the local swelling much worse and should be avoided. Mark the affected area of the limb with an ink marker so that improvement or worsening can be easily noted as time passes. Save whatever intravenous equipment and drug bags are present initially so that the offending agent and circumstances of extravasation can be clearly and thoughtfully assessed. Injection of antidote material into the affected area may be occasionally indicated for specific cases (i.e., hydrofluoric acid or powerful vasoconstrictor extravasations), but in most cases such injections should be avoided because they will only increase local tissue pressures, increase the likelihood of tissue death or vascular compromise, and inconsistently reach the offending agent.

Surgical intervention is an immediate requirement if compartment syndrome or compromise of a major vessel is present. Surgical drainage and decompression of an extravasation injury is also helpful if large volumes of agent are involved, or if the offending agent is a vesicant and the necrosis interval has not yet expired. Once this interval has passed, surgical intervention may be better delayed until clear demarcation of dead tissue has occurred. After thorough debridement of dead tissue, flap coverage or other complex reconstructive procedures may be warranted based on the size of the remaining soft tissue defect.

Nonsurgical Management

This patient presented with a severe, acute left forearm compartment syndrome. All circumferential appliances and intravenous lines were removed from the affected extremity, including the blood pressure cuff, hospital identification bracelet, and 20-gauge angiocatheter. This situation represented a surgical emergency, and all other immediate care required operative intervention.

Surgical Management

The patient was taken to the operating room immediately for emergency fas-ciotomies. A dorsal, longitudinal incision was made from the lateral epicondyle to the mid-carpus, and the dorsal forearm fascia was completely released. A palmar incision was then performed, from the antecubital region to the mid-palm in the hand. The lacertus fibrosus was released, as well as the entire volar forearm fascia. The deep volar compartment was also explored and the fascia overlying the deep volar muscle layer was released. Distally, a carpal tunnel release was also performed (Figs. 26-4 and 26-5).

Upon release of these compartments, ~250 cc of clear fluid was drained from the wounds. Laboratory analysis of this fluid suggested it was a mixture of plasma and

Chemotherapy Extravasation

r- "if / i r r i i r r ■ i- i Figure 26-5. The dorsal surface of the left forearm immediately

Figure 26-4. The palmar surface of the left forearm immediately rnr-r,, r following fasciotomy.

following fasciotomy.

r- "if / i r r i i r r ■ i- i Figure 26-5. The dorsal surface of the left forearm immediately

Figure 26-4. The palmar surface of the left forearm immediately rnr-r,, r following fasciotomy.

following fasciotomy.

electrolyte solution. Neither the dorsal nor palmar forearm and wrist incisions could be closed primarily and no attempt was made to do so.

Postoperative Care

The patient returned to the operating room multiple times over the next 3 weeks for wound debridements. After the swelling subsided and the wounds were stable, meshed full-thickness skin grafts were applied for soft tissue coverage.

Analysis of Case

In the case history presented, the patient suffered a major extravasation injury from electrolyte solution intended to replace lost volume from bleeding. Several factors made this extravasation injury particularly severe. First, the patient had epinephrine infused with the electrolyte solution, which as an extravasant acted as a local vasoconstrictor and greatly worsened local ischemia. Second, because the patient was obtunded, recognition of the injury was significantly delayed and the patient developed a compartment syndrome, probably due both to the amount of fluid ex-travasated as well as to the vasoconstrictive nature of the agent. Third, the presence of constrictive devices around the extremity also contributed in some fashion to the severity of injury. Not only did the patient have a hospital identification band wrapped tightly around her wrist, the frequent blood pressures that were taken with an automatic cuff situated at the upper left arm may also have restricted venous outflow and added to congestion in the extremity. It is also noteworthy that an infusion pump was used, which can produce dramatic extravasation effects by forcing fluid into the extremity. All of these factors can add up and produce a more severe injury than would have otherwise occurred with intravenous fluid extravasation.

This case also illustrates that the presence of peripheral pulses does not exclude a compartment syndrome or suggest that severe local soft tissue injury is not present. Furthermore, although it may seem obvious, the infusion should be turned off and the intravenous catheter removed immediately once a potential extravasation problem has been identified. Of note in this case presentation is that the patient may have received a significant additional amount of electrolyte and epinephrine solution for some period of time after abnormality first presented in the left forearm because no one bothered to turn off the intravenous line and move it to another location.

Suggested Readings

Benson LS, Sathy MJ, Port RB. Forearm compartment syndrome due to automated injection of computed tomography contrast material. J Orthop Trauma 1996;10: 433-436.

Bowers DG, Lynch JB. Adriamycin extravasation. Plast Reconstr Surg 1978;61: 86-92.

Brown AS, Hoelzer DJ, Piercy SA. Skin necrosis from extravasation of intravenous fluids in children. Plast Reconstr Surg 1979;64:145-150.

Gault DT. Extravasation injuries. Br J Plast Surg 1993;46:91-96.

Larson DL. What is the appropriate management of tissue extravasation by antitumor agents? Plast Reconstr Surg 1985;75:397-402.

Linder RM, Upton J, Osteen R. Management of extensive doxorubicin hydrochloride extravasation injuries. J Hand Surg 1983;8:32-38.

LothTS, Eversmann WW Extravasation injuries in the upper extremity. Clin Orthop 1991;272:248-254.

Loth TS, Eversmann WW. Treatment methods for extravasations of chemothera-peutic agents: a comparative study. J Hand Surg 1986;11A:388-396.

LothTS, Jones DEC. Extravasations of radiographic contrast material in the upper extremity. J Hand Surg 1998;13A:407-410.

Luedke DW, Kennedy PS, Rietschel RL. Histopathogenesis of skin and subcutaneous injury induced by Adriamycin. Plast Reconstr Surg 1979;63:463-465.

Mabee JR, BostwickTL, Burke MK. Iatrogenic compartment syndrome from hypertonic saline injection in Bier block. JEmergMed 1993;12:473-476.

Scuderi N, Onesti MG. Antitumor agents: extravasation, management, and surgical treatment. Ann Plast Surg 1994;32:39-44.

Seyfer AE. Injection and extravasation injuries. In: Hand Surgery Update. Rose-mont, IL: American Academy of Orthopaedic Surgeons; 1996:405-411.

Seyfer AE. Upper extremity injuries due to medications. J Hand Surg 1987;12A: 744-750.

Seyfer AE, Solimando DA. Toxic lesions of the hand associated with chemotherapy. J Hand Surg 1983;8:39-42.

Stanley D, Conolly WB. Iatrogenic injection injuries of the hand and upper limb. J Hand Surg 1992;17B:442-446.

Section VI

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