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Management and Prevention of Infiltration and Extravasation Injury
Symposium on New Methods of Treatment of Gastrointestinal Disease
Management and Prevention of
Infiltration and Extravasation Injury Dennis J. Lynch, M.D., John C. Key, M.D.,* and Raleigh R. White, IV, M.D.
Unfortunately, wounds that occur in the hospital setting are not restricted to the carefully prepared elective surgical patient. Our therapeutic armamentarium of life-saving agents includes a number of potentially tissue-toxic substances that are capable of inducing disabling and life-threatening iatrogenic injury when the delivery system fails. This type of wound has been called the intravenous infiltration or extravasation injury and has been presented in several recent articles."- 9, 10 The extravasation wound almost always occurs in the seriously ill patient in a medical or surgical intensive care setting. These patients are often hypoproteinemic, anemic, and vitamin deficient. Their treatments may include adrenocortical steroids, chemotherapeutic agents, or even radiation. It is not at all uncommon for them to harbor virulent forms of microorganisms which will secondarily invade the iatrogenic wound. The extravasation wound is truly a complicating and discouraging event in a patient with little ability to muster the defenses to demarcate, separate, and heal an area of deep necrosis resulting at a failed intravenous site. The extravasation wound results from a combination of adverse events which include agent osmolality, tissue toxicity, vasospasticity, infusion pressure, tissue pressure, and regional anatomic peculiarity. The clinical evaluation of these wounds is difficult since skin involvement is not a reliable indicator of involvement of the subcutaneous fat and fascia. The toxic agent provides the simplest method of classifying the
From the Division of Plastic Surgery, Scott and White Clinic, Temple, Texas ':'Resident in Surgery, Scott and White Clinic, Temple, Texas
Surgical Clinics of North America - Vol. 59, No.5, October 1979
939
940
DENNIS
J.
LYNCH ET AL.
various extravasation injuries. Hyperosmolar solutions, vasopressor agents, and chemotherapeutic drugs are the cause of the most frequently encountered wounds. Several examples of these problems are illustrated with clinical cases. One unusual case resulting in an intraarterial injection is also discussed. The recurring theme in each of the cases presented is a failure in the agent delivery system resulting in patient injury and prolonged morbidity and hospitalization. Hopefully, an awareness of the common pitfalls in agent delivery systems will result in some degree of prevention.
HYPEROSMOLAR AGENTS The infant intensive care unit is an area of highly specialized care within the hospital that has adapted a number of ingenious devices to provide life-saving care for the multiple problems associated with prematurity (Fig. 1). Two of these devices that have a potential for producingwound complications are the scalp vein needle and the intravenous constant infusion pump. A popular nutritional replacement in these small infants is a 12 per cent solution of glucose and amino acid given through a peripheral vein with a small scalp vein needle and a constant infusion pump attached to control the rate of administration." Undoubtedly, this has been a successful method for the neonatologist and has frequently avoided the use of operative placement of a central venous catheter. However, failure at the' site of vein cannulation results in extensive extravasation of hyperosmolar solution. This is pumped widely into the subcutaneous tissue and ultimately increases the tissue pressure of the limb, increasing the potential for ischemia. Progressive edema results from an infusion of extracellular fluid into the tissue area to balance the hyperosmolar agent. Tissue necrosis is the end result of this combination of adverse events. The extent of this necrosis depends on the time it takes for the hospital staff to identify the failed intravenous site. Unfortunately, the most common sites involved are those where the superficial veins are most readily available. These include the dorsum of the hand, the forearm, and the foot. In these areas, there is relatively little soft tissue protection for the underlying tendons and other vital structures. It is not at all uncommon for these wounds to result in tendon exposure and a complex wound healing problem. In several particularly critical infants, multiple anatomic areas were injured because of a prolonged need for this type of feeding. The extravasation wound evolves slowly. Initially, the swelling at the intravenous site is obvious but it may take another 24 hours for darkening to appear in the skin and for there to be some evidence of tissue injury. In the ensuing two weeks, the edema decreases and an obvious, black eschar appears on the skin surface. By two weeks, the wound is usually demarcated and if debridement is done, the extent of
INFILTRATION AND EXTRAVASATION INJURY
941
Figure 1. In the neonatal intensive care unit, malnutrition, scalp vein needles and infusion pumps are the risk factors associated with an extravasation injury. '
necrosis of subcutaneous fat will be found to extend well beyond the area of skin eschar. Multiple debridements are usually required to prepare these areas for skin grafting and final healing may be achieved only after approximately one month, even with aggressive surgical treatment (Fig. 2). Most of these injured infants have respiratory distress syndrome. Surgery and general anesthesia are not reasonable choices for most of them. The majority of these wounds will heal by secondary intention if the wound is treated like a third degree burn and protected from secondary bacterial invasion. Topical antibacterial agents such as Betadine and Silvadene will penetrate the eschar and provide this protection. Of course, it is ultimately the wound healing process of contraction which produces the healing and has the adverse consequence of contracture. On the dorsum of the hand or the foot, this will frequently require secondary revisional surgery at a later date with skin grafts or pedicle flap coverage.
942
DENNIS
J.
LYNCH ET AL.
Figure 2. A, Skin necrosis occurred in a small infant two weeks following infiltration of a hypertonic nutritional solution delivered through an infusion pump and peripheral scalp vein needle. B, Necrosis involves the subcutaneous fat and paratenon. Subsequent debridement exposed the extensor tendons. C, A heterograft dressing covers the exposed extensor tendons. D, One month after injury, healing was completed with a skin graft. The degree of wound contraction is severe and will require secondary revision.
INFILTRATION AND EXTRAVASATION INJURY
943
CALCIUM Calcium gluconate is another agent frequently used on the infant intensive care unit which has a tendency to produce skin necrosis. Its process of evolution is similar to that of a hyperosmolar wound. ·An indurated mass occurs at the failed intravenous site and this mass can usually be demonstrated to contain soft tissue calcification. Skin necrosis also evolves slowly and usually will heal by secondary intention. The emergent intravenous push of a syringe full of calcium gluconate is particularly likely to produce these injuries."
VASOPRESSOR AGENTS The adult intensive care unit has its share of hazardous resuscitative agents. The use of the central venous line for hyperalimentation makes hyperosmolar injury a rare occurrence. On the other hand, agents such as norepinephrine and epinephrine do occasionally produce skin necrosis when given by insecure routes during the organized chaos of cardiopulmonary resuscitation or when given by slow infusion pump through an insecure intravenous catheter. The resulting necrosis in this situation is presumably related to the intense vasospasm produced by these agents. Since the phenomenon of vasospasm is usually reversible, there must also be some relationship to the time over which the agent and .its diluent is pumped into the subcutaneous tissues. Certainly, the extent of necrosis is related to the surface area infused with the agent. The two clinical cases shown illustrate these points (Figs. 3 and 4). In these wounds, the skin necrosis is also less extensive than the subcutaneous injury and is slow to evolve. In the patient with the severe dorsal hand injury the extensor aponeurosis was destroyed and the underlying extensor tendons were exposed (see Fig. 3). Extensor function was preserved by a series of early debridements and biologic dressings to provide temporary cover until the wound was ready for definitive repair. The definitive coverage was provided with a standard groin flap. The application of the Millard crane principle allowed early mobilization of a stiff hand and reduction of soft tissue volume on the dorsum of the hand to avoid bulky flap coverage." In the patient with the extensive neck wound, necrosis involved the periosteum and resulted in bone exposure (see Fig. 4). Unfortunately, it also serves as a reminder that severe wound complications in a patient with a prosthetic valve frequently result in sepsis and death.
ANTITUMOR AGENTS The oncologist dispenses a variety of agents which produce the desired result of cellular death. Drugs such as 5-fluorouracil, mitomycin, and vincristine have all been implicated as causes of tissue necrosis
Figure 3. A, Three weeks after a coronary bypass operation, necrosis is present over the dorsum of the hand and forearm with involvement of the extensor tendons. On the first postoperative day, an infusion of epinephrine infiltrated over a 12 hour period. B, Three weeks after the injury, a groin pedicle flap was applied. C, Two weeks later, the Millard crane principle was applied.' The skin portion of the flap was removed after two weeks, leaving the subcutaneous tissue to provide a vascularized be d for a skin graft. D, The final result at six weeks after injury was good cosmesis and full range of motion.
Figure 4. Following mitral valve replacement, this patient experienced infiltration of an infusion of epinephrine tha t was administered with an infusion pump and external jugular catheter. The resulting necrosis was deep and required debridement. At one month after the injury, the clavicle was exposed. Death resulted from Pseudomonas sepsis.
944
INFILTRATION AND EXTRAVASATION INJURY
945
and indolent wounds. Doxorubicin hydrochloride (Adriamycin) is a newer chemotherapeutic agent of the antibiotic type which has found a wide application in breast cancer, lymphoma, ovarian carcinoma, and sarcoma. It produces the most aggressive and least responsive necrotic lesion in this group and everyone utilizing the agent should be familiar with this effect.": 9 Extravasation of Adriamycin produces severe chemical cellulitis with immediate and persistent pain in the wound (Fig. 5). Rudolph" and Bowers" have clearly demonstrated that this injury differs from other extravasation types in that wound healing is inhibited and demarcation occurs very slowly if at all. Progressive ulceration has been observed in these wounds treated conservatively over several months.
Figure 5. A, Deep progressive, and painful necrosis occurred in the antecubital fossa of this patient following direct injection of Adriamycin. B, After the third excision, it was apparent that necrosis of the deep fascia overlying the neurovascular bundle had occurred. C, A mesh skin graft was placed for final coverage after heterografts had shown good wound adherence. D and E, Total time for wound healing was eight weeks. The final wound coverage has remained stable and provided a functional result. Progression of the tumor became apparent during wound healing and a course of radiation therapy was required. Adriamycin was discontinued.
946
DENNIS
J.
LYNCH ET AL.
The necrosis frequently involves periosteum, paratenon, and fascia. The progression of the lesion has been theorized to be related to the release of tissue-bound Adriamycin from the necrotic tissue to come in contact with living tissue at the wound margin. Because the necrosis is progressive, early debridement has become the standard treatment for this lesion. Although the drug has some fluorescent quality, it is not enough to be helpful in planning these excisions with the use of ultraviolet light. Several debridements are usually required before the wound can finally be treated with either a skin graft or pedicle flap cover. The decision to obtain the best coverage with the use of a multistaged pedicle flap must be tempered in these patients by the ultimate prognosis related to the tumor. In patients with advanced disease, a less stable cover might be traded for an earlier hospital dismissal with more freedom of daily activity. One of the more fascinating aspects of injury caused by Adriamycin is the ability of the drug to produce a recall phenomenon when it is readministered to a patient who has previously had an area of tissue necrosis." While this has not been personally observed, it has been reported that breakdown can occur in an area previously injured by Adriamycin or radiation." It is not clear whether an excised wound caused by Adriamycin and healed with a skin graft or pedicle flap will react in this way. However, when the wound has been extensive and difficult to heal and skin grafts are placed on vital structures, it is probably prudent to discontinue Adriamycin therapy. Of course, this may result in a resurgence of activity in the tumor which had previously been held in abeyance. The patient shown required a course of radiation treatment after the tumor metastasis under treatment more than doubled in size during the period of wound healing (see Fig. 5). Discontinuance of this drug is clearly a life-threatening event for many of these patients. Direct intravenous injection of Adriamycin with syringe and needle is an extremely hazardous maneuver.
INTRA-ARTERIAL INJECTION When a syringe full of medication is injected directly into a vascular structure to achieve a rapid result, there is always the danger that the injection will be intra-arterial. This possibility is increased in those infamous, uncooperative emergency room patients with "rolling" or "no" vein syndrome. An intra-arterial injection of diazepam (Valium) is illustrated (Fig. 6). The disastrous results of this so-called "hand trip" have been well documented in drug addicts with loss of limb as the common denominator. 2 Early experiences with this type of injury were reported by anesthesiologists with the inadvertent arterial injection of thiopental (Pentothal). This agent has been utilized in research studies on the pathogenesis of arterial injection." Vasospasm is only a transient phenomenon and not a likely cause of tissue necrosis. A chemical vasculitis with intimal damage and subsequent thrombosis has been ob-
947
INFILTRATION AND EXTRAVASATION INJURY
B
Figure 6 . A , Intra-arterial injection seen 72 hours after direct injection of diazepam (Valium) into the antecubital space. Cyano is, pain, and coolness with anesthesia of the fourth and fifth distal volar pads were present. Doppler examination demonstrated no flow in the digital vessels of these fingers . Early treatment included stellate ganglion block, salicylates, and low molecula r weight dextran . B. At three weeks after the injury demarcation was complete. C. Four weeks after the injury ray amputation of the small finger and simple amputation of the distal ring finger were required . The total time required for healing was three months.
served in the experimental animal and is the pathophysiologic state which must be reversed by any appropriate treatment method. Certainly, the clinical experience with injury caused by intraarterial injection has been disappointing. This has been particularly true in drug addicts and in those patients in whom therapy was instituted late. Measures such as sympathetic block, fasciotomy, anticoagulation, and local limb care can all be helpful in preventing extension of thrombosis. Occasionally, a good result will be obtained with these techniques, but just as frequently they will fail. Kartchner has described the use of intra-arterial thrombolysin and achieved a few good clinical results. 6 Since this directly attacks the pathogenesis of the lesion, it may deserve wider application.
DENNIS
948
J.
LYNCH ET AL.
PREVENTION The extravasation wound produces impressive morbidity in terms of pain, prolonged healing, potential mortality, and occasional legal entanglement. Its accidental nature is an embarrassment to any conscientious hospital staff, but in today's crash cart practice of medicine, it is probably not completely preventable. However, there are several aspects of intravenous therapy that are particularly hazardous and deserve special recognition. In the delivery of intravenous medications, the best technique is utilization of a secure vein cannula with a small catheter or scalp vein needle. Multiple puncture holes in the vein and an obstructed venous system such as occurs on the arm on the side of a mastectomy should be avoided. Sites on the dorsum of the hand or foot should be avoided, especially when the agent has a known tissue toxicity. The agent needs to be diluted with the recommended solution and given at a slow rate through an intravenous line that is capable of rapid flow rates. The site needs to be observed and the flow discontinued at any sign of patient discomfort. Nursing teams for chemotherapeutic agents and intravenous administration have a consistency that allows for a safe delivery of even the most toxic agents (Fig. 7). A well cannulated vein can extravasate solution when enough pressure is applied to the delivery of the agent. The standard constant infusion pump continues to deliver the agent against considerable in-
Figure 7. Prevention is better than treatment. The best insurance against extravasation injury is a secure, free-flowing venous cannulation With administration of the agent being supervised by a nurse familiar with the type of agent being utilized.
INFILTRATION AND EXTRAVASATION INJURY
949
travenous and tissue pressures. A delivery system with a pump mechanism in line must be watched very carefully, particularly when a peripheral vein is being utilized. The human pump seems to be the most frequent offender in the production of extravasation injury. The expedient therapist who approaches his patient with syringe, needle, and tourniquet in hand must be viewed with skepticism. The risk of extravasation is great in this situation and is not justified except in a life-threatening emergency. Hopefully, knowledge of the severity of extravasation injury will encourage safe agent delivery in all clinical situations.
REFERENCES 1. Andrassy, R. J.: Pediatric nutrition. Contemp. Surg. 14 :23-27, 1979. 2. Blackwell, S. J., Huang, T. T., and Lewis, S. R.: Intra-arterial drug abuse. Tex. Med. 74:64~8, 1978. 3. Bowers, D. G., and Lynch, J. B.: Adriamycin extravasation. Plast. Reconstr. Surg. 61 :86-92, 1978. 4. Buckspan, G. S., et al.: Intra-arterial drug injury: Studies of etiology and potential treatment. J. Surg. Res. 24 :294-301, 1978. 5. Donaldson, S. S., Glick, J. M., and Wilbur, J. R.: Adriamycin activating a recall phenomenon after radiation therapy. Ann. Intern. Med. 81 :407-408, 1974. 6. Kartchner, M. M., and Wilcox, W. G.: Thrombolysis of palmar and digital arterial thrombosis by intra-arterial thrombolysin. J. Hand Surg. 1 :67-74, 1976. 7. Millard, R. D.: The crane principle for transport of subcutaneous tissue. Plast. Reconstr. Surg. 43 :451-462, 1969. 8. Roberts, J. R.: Cutaneous and subcutaneous complications of calcium infusions. J. Am. CoIl. Emerg. Phys. 6:16-20,1977. 9. Rudolph, R., Stein, R. S., and Patillo, R. A.: Skin ulcers due to Adriamycin. Cancer, 38:1087-1094, 1976. 10. Yosowitz, P., Eckland, D. A., Shaw, R. C., et al.: Peripheral intravenous infiltration necrosis. Ann. Surg. 182:553-556, 1975.
Scott and White Clinic Temple, Texas 76501
Management and Prevention of
Infiltration and Extravasation Injury Dennis J. Lynch, M.D., John C. Key, M.D.,* and Raleigh R. White, IV, M.D.
Unfortunately, wounds that occur in the hospital setting are not restricted to the carefully prepared elective surgical patient. Our therapeutic armamentarium of life-saving agents includes a number of potentially tissue-toxic substances that are capable of inducing disabling and life-threatening iatrogenic injury when the delivery system fails. This type of wound has been called the intravenous infiltration or extravasation injury and has been presented in several recent articles."- 9, 10 The extravasation wound almost always occurs in the seriously ill patient in a medical or surgical intensive care setting. These patients are often hypoproteinemic, anemic, and vitamin deficient. Their treatments may include adrenocortical steroids, chemotherapeutic agents, or even radiation. It is not at all uncommon for them to harbor virulent forms of microorganisms which will secondarily invade the iatrogenic wound. The extravasation wound is truly a complicating and discouraging event in a patient with little ability to muster the defenses to demarcate, separate, and heal an area of deep necrosis resulting at a failed intravenous site. The extravasation wound results from a combination of adverse events which include agent osmolality, tissue toxicity, vasospasticity, infusion pressure, tissue pressure, and regional anatomic peculiarity. The clinical evaluation of these wounds is difficult since skin involvement is not a reliable indicator of involvement of the subcutaneous fat and fascia. The toxic agent provides the simplest method of classifying the
From the Division of Plastic Surgery, Scott and White Clinic, Temple, Texas ':'Resident in Surgery, Scott and White Clinic, Temple, Texas
Surgical Clinics of North America - Vol. 59, No.5, October 1979
939
940
DENNIS
J.
LYNCH ET AL.
various extravasation injuries. Hyperosmolar solutions, vasopressor agents, and chemotherapeutic drugs are the cause of the most frequently encountered wounds. Several examples of these problems are illustrated with clinical cases. One unusual case resulting in an intraarterial injection is also discussed. The recurring theme in each of the cases presented is a failure in the agent delivery system resulting in patient injury and prolonged morbidity and hospitalization. Hopefully, an awareness of the common pitfalls in agent delivery systems will result in some degree of prevention.
HYPEROSMOLAR AGENTS The infant intensive care unit is an area of highly specialized care within the hospital that has adapted a number of ingenious devices to provide life-saving care for the multiple problems associated with prematurity (Fig. 1). Two of these devices that have a potential for producingwound complications are the scalp vein needle and the intravenous constant infusion pump. A popular nutritional replacement in these small infants is a 12 per cent solution of glucose and amino acid given through a peripheral vein with a small scalp vein needle and a constant infusion pump attached to control the rate of administration." Undoubtedly, this has been a successful method for the neonatologist and has frequently avoided the use of operative placement of a central venous catheter. However, failure at the' site of vein cannulation results in extensive extravasation of hyperosmolar solution. This is pumped widely into the subcutaneous tissue and ultimately increases the tissue pressure of the limb, increasing the potential for ischemia. Progressive edema results from an infusion of extracellular fluid into the tissue area to balance the hyperosmolar agent. Tissue necrosis is the end result of this combination of adverse events. The extent of this necrosis depends on the time it takes for the hospital staff to identify the failed intravenous site. Unfortunately, the most common sites involved are those where the superficial veins are most readily available. These include the dorsum of the hand, the forearm, and the foot. In these areas, there is relatively little soft tissue protection for the underlying tendons and other vital structures. It is not at all uncommon for these wounds to result in tendon exposure and a complex wound healing problem. In several particularly critical infants, multiple anatomic areas were injured because of a prolonged need for this type of feeding. The extravasation wound evolves slowly. Initially, the swelling at the intravenous site is obvious but it may take another 24 hours for darkening to appear in the skin and for there to be some evidence of tissue injury. In the ensuing two weeks, the edema decreases and an obvious, black eschar appears on the skin surface. By two weeks, the wound is usually demarcated and if debridement is done, the extent of
INFILTRATION AND EXTRAVASATION INJURY
941
Figure 1. In the neonatal intensive care unit, malnutrition, scalp vein needles and infusion pumps are the risk factors associated with an extravasation injury. '
necrosis of subcutaneous fat will be found to extend well beyond the area of skin eschar. Multiple debridements are usually required to prepare these areas for skin grafting and final healing may be achieved only after approximately one month, even with aggressive surgical treatment (Fig. 2). Most of these injured infants have respiratory distress syndrome. Surgery and general anesthesia are not reasonable choices for most of them. The majority of these wounds will heal by secondary intention if the wound is treated like a third degree burn and protected from secondary bacterial invasion. Topical antibacterial agents such as Betadine and Silvadene will penetrate the eschar and provide this protection. Of course, it is ultimately the wound healing process of contraction which produces the healing and has the adverse consequence of contracture. On the dorsum of the hand or the foot, this will frequently require secondary revisional surgery at a later date with skin grafts or pedicle flap coverage.
942
DENNIS
J.
LYNCH ET AL.
Figure 2. A, Skin necrosis occurred in a small infant two weeks following infiltration of a hypertonic nutritional solution delivered through an infusion pump and peripheral scalp vein needle. B, Necrosis involves the subcutaneous fat and paratenon. Subsequent debridement exposed the extensor tendons. C, A heterograft dressing covers the exposed extensor tendons. D, One month after injury, healing was completed with a skin graft. The degree of wound contraction is severe and will require secondary revision.
INFILTRATION AND EXTRAVASATION INJURY
943
CALCIUM Calcium gluconate is another agent frequently used on the infant intensive care unit which has a tendency to produce skin necrosis. Its process of evolution is similar to that of a hyperosmolar wound. ·An indurated mass occurs at the failed intravenous site and this mass can usually be demonstrated to contain soft tissue calcification. Skin necrosis also evolves slowly and usually will heal by secondary intention. The emergent intravenous push of a syringe full of calcium gluconate is particularly likely to produce these injuries."
VASOPRESSOR AGENTS The adult intensive care unit has its share of hazardous resuscitative agents. The use of the central venous line for hyperalimentation makes hyperosmolar injury a rare occurrence. On the other hand, agents such as norepinephrine and epinephrine do occasionally produce skin necrosis when given by insecure routes during the organized chaos of cardiopulmonary resuscitation or when given by slow infusion pump through an insecure intravenous catheter. The resulting necrosis in this situation is presumably related to the intense vasospasm produced by these agents. Since the phenomenon of vasospasm is usually reversible, there must also be some relationship to the time over which the agent and .its diluent is pumped into the subcutaneous tissues. Certainly, the extent of necrosis is related to the surface area infused with the agent. The two clinical cases shown illustrate these points (Figs. 3 and 4). In these wounds, the skin necrosis is also less extensive than the subcutaneous injury and is slow to evolve. In the patient with the severe dorsal hand injury the extensor aponeurosis was destroyed and the underlying extensor tendons were exposed (see Fig. 3). Extensor function was preserved by a series of early debridements and biologic dressings to provide temporary cover until the wound was ready for definitive repair. The definitive coverage was provided with a standard groin flap. The application of the Millard crane principle allowed early mobilization of a stiff hand and reduction of soft tissue volume on the dorsum of the hand to avoid bulky flap coverage." In the patient with the extensive neck wound, necrosis involved the periosteum and resulted in bone exposure (see Fig. 4). Unfortunately, it also serves as a reminder that severe wound complications in a patient with a prosthetic valve frequently result in sepsis and death.
ANTITUMOR AGENTS The oncologist dispenses a variety of agents which produce the desired result of cellular death. Drugs such as 5-fluorouracil, mitomycin, and vincristine have all been implicated as causes of tissue necrosis
Figure 3. A, Three weeks after a coronary bypass operation, necrosis is present over the dorsum of the hand and forearm with involvement of the extensor tendons. On the first postoperative day, an infusion of epinephrine infiltrated over a 12 hour period. B, Three weeks after the injury, a groin pedicle flap was applied. C, Two weeks later, the Millard crane principle was applied.' The skin portion of the flap was removed after two weeks, leaving the subcutaneous tissue to provide a vascularized be d for a skin graft. D, The final result at six weeks after injury was good cosmesis and full range of motion.
Figure 4. Following mitral valve replacement, this patient experienced infiltration of an infusion of epinephrine tha t was administered with an infusion pump and external jugular catheter. The resulting necrosis was deep and required debridement. At one month after the injury, the clavicle was exposed. Death resulted from Pseudomonas sepsis.
944
INFILTRATION AND EXTRAVASATION INJURY
945
and indolent wounds. Doxorubicin hydrochloride (Adriamycin) is a newer chemotherapeutic agent of the antibiotic type which has found a wide application in breast cancer, lymphoma, ovarian carcinoma, and sarcoma. It produces the most aggressive and least responsive necrotic lesion in this group and everyone utilizing the agent should be familiar with this effect.": 9 Extravasation of Adriamycin produces severe chemical cellulitis with immediate and persistent pain in the wound (Fig. 5). Rudolph" and Bowers" have clearly demonstrated that this injury differs from other extravasation types in that wound healing is inhibited and demarcation occurs very slowly if at all. Progressive ulceration has been observed in these wounds treated conservatively over several months.
Figure 5. A, Deep progressive, and painful necrosis occurred in the antecubital fossa of this patient following direct injection of Adriamycin. B, After the third excision, it was apparent that necrosis of the deep fascia overlying the neurovascular bundle had occurred. C, A mesh skin graft was placed for final coverage after heterografts had shown good wound adherence. D and E, Total time for wound healing was eight weeks. The final wound coverage has remained stable and provided a functional result. Progression of the tumor became apparent during wound healing and a course of radiation therapy was required. Adriamycin was discontinued.
946
DENNIS
J.
LYNCH ET AL.
The necrosis frequently involves periosteum, paratenon, and fascia. The progression of the lesion has been theorized to be related to the release of tissue-bound Adriamycin from the necrotic tissue to come in contact with living tissue at the wound margin. Because the necrosis is progressive, early debridement has become the standard treatment for this lesion. Although the drug has some fluorescent quality, it is not enough to be helpful in planning these excisions with the use of ultraviolet light. Several debridements are usually required before the wound can finally be treated with either a skin graft or pedicle flap cover. The decision to obtain the best coverage with the use of a multistaged pedicle flap must be tempered in these patients by the ultimate prognosis related to the tumor. In patients with advanced disease, a less stable cover might be traded for an earlier hospital dismissal with more freedom of daily activity. One of the more fascinating aspects of injury caused by Adriamycin is the ability of the drug to produce a recall phenomenon when it is readministered to a patient who has previously had an area of tissue necrosis." While this has not been personally observed, it has been reported that breakdown can occur in an area previously injured by Adriamycin or radiation." It is not clear whether an excised wound caused by Adriamycin and healed with a skin graft or pedicle flap will react in this way. However, when the wound has been extensive and difficult to heal and skin grafts are placed on vital structures, it is probably prudent to discontinue Adriamycin therapy. Of course, this may result in a resurgence of activity in the tumor which had previously been held in abeyance. The patient shown required a course of radiation treatment after the tumor metastasis under treatment more than doubled in size during the period of wound healing (see Fig. 5). Discontinuance of this drug is clearly a life-threatening event for many of these patients. Direct intravenous injection of Adriamycin with syringe and needle is an extremely hazardous maneuver.
INTRA-ARTERIAL INJECTION When a syringe full of medication is injected directly into a vascular structure to achieve a rapid result, there is always the danger that the injection will be intra-arterial. This possibility is increased in those infamous, uncooperative emergency room patients with "rolling" or "no" vein syndrome. An intra-arterial injection of diazepam (Valium) is illustrated (Fig. 6). The disastrous results of this so-called "hand trip" have been well documented in drug addicts with loss of limb as the common denominator. 2 Early experiences with this type of injury were reported by anesthesiologists with the inadvertent arterial injection of thiopental (Pentothal). This agent has been utilized in research studies on the pathogenesis of arterial injection." Vasospasm is only a transient phenomenon and not a likely cause of tissue necrosis. A chemical vasculitis with intimal damage and subsequent thrombosis has been ob-
947
INFILTRATION AND EXTRAVASATION INJURY
B
Figure 6 . A , Intra-arterial injection seen 72 hours after direct injection of diazepam (Valium) into the antecubital space. Cyano is, pain, and coolness with anesthesia of the fourth and fifth distal volar pads were present. Doppler examination demonstrated no flow in the digital vessels of these fingers . Early treatment included stellate ganglion block, salicylates, and low molecula r weight dextran . B. At three weeks after the injury demarcation was complete. C. Four weeks after the injury ray amputation of the small finger and simple amputation of the distal ring finger were required . The total time required for healing was three months.
served in the experimental animal and is the pathophysiologic state which must be reversed by any appropriate treatment method. Certainly, the clinical experience with injury caused by intraarterial injection has been disappointing. This has been particularly true in drug addicts and in those patients in whom therapy was instituted late. Measures such as sympathetic block, fasciotomy, anticoagulation, and local limb care can all be helpful in preventing extension of thrombosis. Occasionally, a good result will be obtained with these techniques, but just as frequently they will fail. Kartchner has described the use of intra-arterial thrombolysin and achieved a few good clinical results. 6 Since this directly attacks the pathogenesis of the lesion, it may deserve wider application.
DENNIS
948
J.
LYNCH ET AL.
PREVENTION The extravasation wound produces impressive morbidity in terms of pain, prolonged healing, potential mortality, and occasional legal entanglement. Its accidental nature is an embarrassment to any conscientious hospital staff, but in today's crash cart practice of medicine, it is probably not completely preventable. However, there are several aspects of intravenous therapy that are particularly hazardous and deserve special recognition. In the delivery of intravenous medications, the best technique is utilization of a secure vein cannula with a small catheter or scalp vein needle. Multiple puncture holes in the vein and an obstructed venous system such as occurs on the arm on the side of a mastectomy should be avoided. Sites on the dorsum of the hand or foot should be avoided, especially when the agent has a known tissue toxicity. The agent needs to be diluted with the recommended solution and given at a slow rate through an intravenous line that is capable of rapid flow rates. The site needs to be observed and the flow discontinued at any sign of patient discomfort. Nursing teams for chemotherapeutic agents and intravenous administration have a consistency that allows for a safe delivery of even the most toxic agents (Fig. 7). A well cannulated vein can extravasate solution when enough pressure is applied to the delivery of the agent. The standard constant infusion pump continues to deliver the agent against considerable in-
Figure 7. Prevention is better than treatment. The best insurance against extravasation injury is a secure, free-flowing venous cannulation With administration of the agent being supervised by a nurse familiar with the type of agent being utilized.
INFILTRATION AND EXTRAVASATION INJURY
949
travenous and tissue pressures. A delivery system with a pump mechanism in line must be watched very carefully, particularly when a peripheral vein is being utilized. The human pump seems to be the most frequent offender in the production of extravasation injury. The expedient therapist who approaches his patient with syringe, needle, and tourniquet in hand must be viewed with skepticism. The risk of extravasation is great in this situation and is not justified except in a life-threatening emergency. Hopefully, knowledge of the severity of extravasation injury will encourage safe agent delivery in all clinical situations.
REFERENCES 1. Andrassy, R. J.: Pediatric nutrition. Contemp. Surg. 14 :23-27, 1979. 2. Blackwell, S. J., Huang, T. T., and Lewis, S. R.: Intra-arterial drug abuse. Tex. Med. 74:64~8, 1978. 3. Bowers, D. G., and Lynch, J. B.: Adriamycin extravasation. Plast. Reconstr. Surg. 61 :86-92, 1978. 4. Buckspan, G. S., et al.: Intra-arterial drug injury: Studies of etiology and potential treatment. J. Surg. Res. 24 :294-301, 1978. 5. Donaldson, S. S., Glick, J. M., and Wilbur, J. R.: Adriamycin activating a recall phenomenon after radiation therapy. Ann. Intern. Med. 81 :407-408, 1974. 6. Kartchner, M. M., and Wilcox, W. G.: Thrombolysis of palmar and digital arterial thrombosis by intra-arterial thrombolysin. J. Hand Surg. 1 :67-74, 1976. 7. Millard, R. D.: The crane principle for transport of subcutaneous tissue. Plast. Reconstr. Surg. 43 :451-462, 1969. 8. Roberts, J. R.: Cutaneous and subcutaneous complications of calcium infusions. J. Am. CoIl. Emerg. Phys. 6:16-20,1977. 9. Rudolph, R., Stein, R. S., and Patillo, R. A.: Skin ulcers due to Adriamycin. Cancer, 38:1087-1094, 1976. 10. Yosowitz, P., Eckland, D. A., Shaw, R. C., et al.: Peripheral intravenous infiltration necrosis. Ann. Surg. 182:553-556, 1975.
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