Major Intravenous Extravasation Injuries Joseph Upton, MD, Boston, Massachusetts John 6. Mulliken, MD, Boston, Massachusetts Joseph E. Murray, MD, Boston, Massachusetts

Protracted intravenous administration of maintenance fluids, blood and blood products, chemotherapeutic agents and medications causes inevitable extravasation injuries. The majority of these infiltrations are recognized early, remain well localized, and heal spontaneously. However, with any active surgical, medical, or oncological service, several patients each year will probably have major extravasation wounds. The clinical treatment of severe extravasation injuries consists of prolonged watchful waiting for healing or eventual demarcation, followed by multiple debridements and wound closure. Patients with these iatrogenic injuries have considerably longer hospital stays and increased morbidity. This is a retrospective study of thirty-one patients with major intravenous extravasation injuries analyzed in terms of causative agents, natural history, treatment, mechanisms of necrosis, and prevention. Material and Methods

Major soft tissue extravasation injuries result in wounds that are sufficiently large to require debridement and

coverage with skin graft, flap, or eventual amputation. Drug addicts were excluded from this study. The thirty-one patients were followed up for at least one year or until the time of death. The patients were treated in five institutions: Yale-New Haven Hospital New Haven, Connecticut; St. Joseph Hospital, Houston, Texas; Eisenhower Medical

From Harvard Medical School, Division of Plastic Surgery, Peter Bent Brigham Hospital, Children’s Hospital Medical Center, Boston, Massachusetts. Reprint requests should be addressed to Joseph Upton, MD, Division of Plastic Svgery, Chilben’s Hospital Medical Center, 300 Longwood Avenue, Boston! Massachusetts 02 115. Presented at the Fifty-Ninth Annual Meeting of the New England Surgical Society, Dixville Notch, New Hampshire, September 29-October 1, 1978.

Volume 137, April 1979

Center, Augusta, Georgia; Roosevelt Hospital, New York City; and Peter Bent Brigham Hospital and Children’s Hospital Medical Center, Boston, Massachusetts. The study extended over a nine year period from 1969 to 1978. The most common agents responsible for soft tissue extravasation injuries were the osmotically-active chemicals and cationic solutions: 30 per cent urea and 10 per cent dextrose solutions, potassium chloride, calcium chloride, calcium gluconate, and amino acid calcium gluceptate-10 per cent dextrose solution. Other causative agents were the vasopressors epinephrine, dopamine, Aramine@, and the cytotoxic agents adriamycin and methotrexate. Misceilaneous agents included thiopental, tetracycline, and Renografinm-60, a contrast dye used for phlebography. These injuries occurred primarily in the pediatric and geriatric patients. (Table I.) Seven patients were younger than age ten years and twelve patients were younger than twenty years. Most of the patients in the 21 to 60 year age group were admitted to the hospital for elective surgical procedures. Nine patients were over sixty-one years of age. The majority of these elderly patients with extravasations were injured during cardiac resuscitation and had preexisting vascular disease or diabetes mellitus. The dorsum of the hand was the most frequent site of injury. (Table II.) The injury usually extended from the extension crease at the wrist to the metacarpophalangeal joint level. Four elderly patients with extensive soft tissue loss exceeding 35 cm2 in area were receiving vasopressor drips for circulatory support. One infant sustained extensive scalp loss while receiving intravenous macronutrients. Three patients had injuries to the dorsum of the foot: two infants receiving antibiotics and an elderly man with preexisting vascular disease who had extravasated contrast dye. The majority of patients were either comatose or under general anesthesia at the time of extravasation injury. The six injuries that occurred during resuscitation for myocardial infarction were predominantly cation agent injuries.

Upton, Mulliken, and Murray

TABLE I

Relation of Age and Extravasation Injuries in Thirty-One Patients

Age WI

No. of Patients

Birth-10 1 l-20 21-30 31-40 41-50 51-60 61-70 71-80

7 5 0 5 1 4 6 3

(Table III.) Four patients sustained extravasation injuries during prolonged general anesthesia; five patients were severely ill and comatose in intensive care units. The extravasation injuries in four patients who were receiving chemotherapy under protocol were related to adriamycin in three patients and to methotrexate in one patient. Four awake adults sustained injuries to the lower extremities through intravenous vasopressor drips for hypotension; three of these patients had a history of venous disease in the lower extremities. Five of the seven children under age ten years were awake at the time of extravasation. Three of these patients were infants, and all were too young to verbalize the discomfort caused by the pain and pressure of the extravasated fluid. Table III documents a 1 to 140 day range of time between the extravasation injury and the request for surgical consultation. The majority of patients were receiving nonsurgical treatment. The extent of soft tissue damage was often underestimated and the extravasation injury was therefore treated conservatively for a period of time in these critically ill patients. Surgical consultations were usually requested between the second and third week after injury when the lateral wound margins were clearly demarcated. In many instances, at the time of consultation it was impossible to determine precisely in retrospect the total millimoles infused, the rate and duration of the infusion (especially with vasopressor drips), and the pH of the administered solutions. Diagnosis. The eventual depth and peripheral extent of the full thickness tissue loss was invariably worse than predicted on the initial examination. The osmotically active and cationic solutions were the most common causative agents and the most unpredictable in relation to an estimation of the eventual extent of tissue loss. The physician was often falsely optimistic when small blisters formed within the epidermis during the first 24 to 48 hours after extravasation, suggesting partial thickness injury. Full thickness loss was the inevitable result. When an extravasation was adjacent to a major artery in the forearm or leg, absent pulses were recorded and documented with Doppler examination. In two patients this “spasm” never resolved and amputation was required. Within five or seven days, the area of extravasation usually appeared as a full thick-

498

TABLE II

Location of Extravasation Injuries

Location Dorsum of hand Anticubital fossa of arm Dorsal forearm Volar wrist and forearm Leg Scalp Dorsum of foot

No. of Injuries’ 19 1 1 4 4 1 3 33’

+ Thirty-one patients had thirty-three extravasation injuries. One man had injuries on the dorsum of both hands, and another had injuries on one hand and one leg.

ness loss, although the eschar remained rather pink in color unless the overlying blisters had been debrided. Extravasations in the forearm and dorsum of the hand were observed carefully for increasing swelling, diminishing pulses and increasing pain with passive extension of the fingers, as indicators of early Volkmann’s ischemic contracture. Penetrating extravasations into the dorsum of the hand caused myonecrosis of the underlying dorsal intrinsic compartments. Prompt decompression of thigh fascial compartments was necessary in several patients [I]. A history of peripheral vascular disease, venous or arterial, diabetes mellitus, and Raynaud’s phenomenon was noted in seven of thirty-one patients and may have predisposed them to extravasation injuries. Several of the patients receiving vasopressor drips reported insensitivity at the time of the infiltration. Diabetic peripheral neuropathy in these patients may account for the insensitivity to extravasation. Two of the four patients with leg infiltrations developed deep vein thrombophlebitis and subsequent pulmonary emboli. Adriamycin (doxorubicin hydrochloride) extravasations were the most insidious [2,3] because they gradually extended and eventually produced indolent ulcers resembling radiation necrosis wounds. Immediately after extravasation, these injuries exhibited a nonblanching, red color with some areas of blistering, which indicated direct deposition of the drug in crystalline form in the dermal and subcutaneous planes. Biopsies of the injured tissue, examined under the fluorescent microscope, demonstrated the true nature of these wounds. Unfortunately, adriamycin crystals in small concentration were difficult to recognize on biopsy. Histologic examination of areas of maximal infiltration demonstrated a noteworthy lack of inflammatory response and absence of dermal circulation. Within four to five days the lateral margins of these wounds demarcated and the eschar darkened. If bacterial infection did not invade the wound, the dry eschar remained for a long period, often months. More frequently, the eschar in the central portion of the extravasation became infected and separated, leaving a recalcitrant nonhealing ulcer. All of the patients injured with cytotoxic agents were on drug protocols that included prednisone, which is known to inhibit the in-

The Amerlcsn Journal of Surgery

Intravenous Extravasation

Injuries

Figure 1. A, seven days after extravasation of 2 ampules of calcium giuconate during a cardiac resuscitation. B, at debrktemsnt ten days after the injury, loss ofparatenon over the central extensor tendons had occurred~ with extensive necros& of underlying fascia and muscle. C, three weeks after the injury the wound was ready for skin grafting, aithough the extensor tendons needed further debridement. 0, at six weeks the central area of necrosis was ready for coverage. E, four months later the wound was healed. Edema in tfte fingers, stiff metatarsophaiangeal andproximai interphaiangeai joints, and loss of four extensor tendons restricted function of the hand.

flammatory response and capillary neovascularization. Many of these patients were also systemically ill. Toxic epidermal necrolysis [4] may often be confused with full thickness extravasation injuries. Large bullae with or without hemorrhage will present at an area of extravasation and may extend extensively from the site of injury. Gram stain of the draining fluid will show gram positive

Volume 137, April 1979

cocci, and Tzanck preparation of the same fluid will show squamous cells. Staphylococci phage type 71 Group 2 usually cause this partial thickness injury, which will heal within two weeks with antistaphylococcal therapy [4]. This severe form of staphylococcal bullous impetigo is uncommon in adults or children unless they are receiving immunosuppressive therapy.

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Upton, Muiiiken, and Murray

TABLE Ill

Clinical Data on Thirty-One Patients

Patient’s Age (yr)/Sex and Admitting Condition

Causative Agent

Circumstance Injury

of Location

Time of Consultation

No. of Operations

2 days

4

10 days

4

9/F, head trauma

30% urea-lo% dextrose solution

During surgery for skull fx

Entire volar wrist and forearm

Fl36, breast abscess, Hx Raynauds phenomenon F/l wk, gastroenteritis M/42, coronary artery disease

KCI

During surgery and in RR; hypokalemia from diuretics Awake in EW

6 X 10” ulcer medial calf

Dorsum of hand

32 days

2

Entire dorsum of forearm; 5 x 10N

14 days

2

F/72, sacral decubitus sepsis, dehydration F/9, craniopharyngioma

KCI

Entire dorsum of arm and forearm

5 days

None

Entire forearm and hand

2 days

4

F/62, pneumonia, diabetes mellitus

KCI

During surgery CABG, multiple puncture sites Infected subclavian catheter; axillary vein thrombosis During surgery and in ICU, radial artery catheter Awake but lethargic on ward

Entire distal volar forearm and wrist

14 days

3

M/52, myocardial infarction

CaCls

Cardiac arrest in ER

Entire dorsum of hand

16 days

5

M/19. head trauma F/60, coronary artery disease

CaCls

Entire dorsum of hand Entire dorsum of hand and wrist

16 days

4

CaC12

During surgery for skull fx During surgery & in ICU for CABG

28 days

3

M/44, cardiac arrhythmia

KCI Ca gluconate

Cardiac arrest in ICU

Dorsum of both hands

M/68, cardiac arrhythmia, abdominal aneurysm M/79, cardiac arrhythmia

Ca gluconate

Cardiac arrest in ICU after aneurysm resection

Entire dorsum of hand

7 days

4

Ca gluconate

Cardiac arrest in ICU; multiple IV puncture

Entire dorsum of hand

18 days

3

M/66, aortic insufficiency, coronary artery disease F/20. chest trauma, respiratory arrest F/5 mo, failure to thrive

Ca gluconate

During surgery & in ICU postop, multiple IV punctures

Entire dorsum of hand

7 days

3

Ca gluconate

Respiratory arrest in EW

Entire dorsum of hand

4 days

4

Amino acid Ca gluceptate 10 % dextrose solution

Newborn care unit

Entire temporal scalp

17 days

4

500

KCI KCI

KCI, hypertonic saline

’

3 days (2 on right hand, 4 on left)

Result Volkman’s contracture; lost ail flexors; median, ulnar nerves spared Deep vein thrombophlebitis

Extensor loss to index and long Extensor loss: index, long, ring, small fingers Complete venous obstruction of arm; died 4 weeks later BE amputation

Stiffness, loss of 3 superficial flexors; median nerve deficit Loss of all extensors, sympathetic dystrophy syndrome Extensor loss: long, ring fingers Significant MP & PIP stiffness, extensor loss: index & long fingers Stiffness, sympathetic dystrophy syndrome Stiffness extensor loss: index, long 8 ring fingers

Extensor loss: thumb, index, long, ring & small fingers Stiffness, residual edema, sympathetic dystrophy syndrome Stiffness; extensor loss: index, long & ring fingers Loss of hair in grafted area

The American Journal 01 Surgery

Intravenous

TABLE III

(continued)

Patient’s Age (yr)/Sex and Admitting Condition

Causative Agent

Extravasation

Injuries

Circumstance Injury

of Location

lime of Consultation

No. of Operations

Result

F/73, COPD, chronic bronchitis, GI bleeding

Aramine

Awake, but hypoxic on ward

Entire dorsum of hand

23 days

4

M/62, inguinal hernia, postop GI bleeding, peripheral vascular symptoms M/62, hypotension

Dopamine

Awake on ward

5X

11”ulcer of right calf

65 days

2

Dopamine

On ward after hypotensive episode

54 days

1 (hand), 2 (les)

Stiffness of hand

F/68, post total joint replacement (knee), rheumatoid arthritis, GI bleeding M/60, cardiac arrhythmia

Dopamine

On ward during GI bleeding

Entire dorsum of left hand; 4 X 6” slough, medial calf 5 X 12” ulcer of calf and dorsum of foot

56 days

3

Superficial deep vein thrombophlebitis

Epinephrine Aramine

Entire anticubital fossa

2 days

0

F/40. fever, pharyngitis

Tetracycline IV

Unconscious during insertion of pacemaker; cardiac arrest Awake on ward

Entire hand

35 days

2

F/2 wk, fever, unknown origin

Tetracycline IV

IV administered in ER as outpatient

Entire dorsum of hand

24 days

4

M/64, phlebitis lower extremity, hyperosmotic coma, diabetes mellitus, pulmonary emboli, peripheral vascular disease F/39, ptosis of breast, Hx Raynaud’s phenomenon

Aenografin-60 (75 cc)

Phlebography X-ray unit

Entire dorsum of foot

140 days

3

Died 2 weeks later (arm would have required AE amputation) Arterial compromise: amputations: index MP, long PIP, ring PIP Extensive MP extension contractures; extensor loss thumb & index finger: princeps pollicis artery lost Increased ischemic pain

Valium

During surgery (mastopexy); under local anesthesia

Vofar wrist & forearm, 4 X 8# segment

24 days

3

F/21, cholecystitis. scleroderma

Valium KCI

Postop in ICU

Entire dorsum of hand

70 days

2

Volume 137, April 1979

in

Stiffness; no MP or PIP motion; sympathetic dystrophy syndrome Increased ischemic pain at rest

Stiffness; acrocyanosis symptoms aggravated; increased cold intolerance Stiffness; all MP’s & PIP’s; 3 nonhealing fingertip ulcers aggravated Raynaud’s symptoms

501

Upton,

TABLE

Mulliken,

III

and Murray

(continued)

Patient’s Age (yr)/Sex and Admitting Condition

Circumstance Injury

Causative Agent

of Location

Time of Consultation

No. of Operations

F/19, open tibia1 fracture, Hx Reynaud’s phenomenon F/22, choriocarcinema M/10, acute leukemia

Thiopentol

Pentathol extravasation during surgery

Volar forearm

4 wk

3

Methotrexate (MOP protocol)

Awake as an inpatient

Dorsum of hand

40 days

3

Adriamycin

IV

Awake in room

Entire dorsum of hand

42 days

6

F/68, oat cell carcinoma of lung

Adriamycin drip

IV

Awake in room

Entire volar wrist 8 forearm

21 days

3

F/11, acute leukemia

Adriamycin drip

IV

Awake but sedated in room

Entire dorsum of foot & ankle

42 days

9

Result Volkman’s ischemic contracture of forearm; amputation of all fingers Stiffness; extensor loss: index & long fingers Extensors saved initially; later EPL rupture Loss of all MP & PIP motion; sympathetic dystrophy syndrome Initially covered with STSG; later reconstruction using cross-like flap during remission

Note: AE = above elbow; BE = below elbow; CABG = coronary artery bypass graft; COPD = chronic obstructive pulmonary disease; EPL = extensor pollicis longus; EW = emergency ward: fx = fracture; GI = gastrointestinal; Hx = history; ICU = intensive care unit; IV = intravenous; MOP = methotrexate Oncovine prednisone drug protocol; MP = metatarsophalangeal; PIP = proximal interphalangeal; postop = postoperatively; RR = recovery room.

Treatment. If the extravasation injury was noted early, the extremity was covered with a light compression dressing, immobilized in the position of “advantage” with the wrist dorsiflexed 30 degrees, the metacarpophalangeal joints flexed 70 degrees and the thumb abducted into the palm and elevated to minimize edema. If arterial compromise or compression syndromes developed in the arm or leg, prompt fascial decompression and debridement of necrotic muscle was necessary. This commonly occurred in the dorsal hand injury sites. In patients too ill to tolerate debridement, treatment consisted of elevation, antibiotics, night splinting and daily motion exercises. When large areas of full thickness loss were clearly demonstrated, prompt debridement of all nonviable tissue and control of any subeschar infection was necessary. Very aggressive and early debridement of cationic (calcium and potassium) and cytotoxic extravasations was encouraged because these injuries, although demarcated at their lateral margins, appeared to extend in depth. Wounds were covered using biologic dressings, split thickness skin grafts, and flaps, if necessary, in the most simple and efficient manner possible. The debilitated condition of many of these patients precluded multistaged flap procedures. The use of local muscle flaps to cover vital structures such as nerves or vessels, followed by split thickness skin coverage, was an effective method of avoiding more complex procedures. At the time of debridement of the eschar, significant bacterial colonization (greater than lo5 bacteria/g of tissue) [5] was documented in twenty-four of thirty-one patients.

502

Gram positive organisms predominated. Four millimeter punch biopsies of the injured tissue for hematoxylin and eosin sections and quantitative bacteriology was helpful in expediting the decision for sharp debridement. Infected wounds were treated with systemic antibiotics, frequent dressing changes, and multiple debridement until the granulating bed was ready for coverage. Extensor tendons on the dorsum of the hand had to be excised if infected or unprotected by vascularized paratenon. The few children with extravasation wounds in this study were newborn infants and were treated conservatively. At the Children’s Hospital Medical Center the inevitable problem of extravasation injuries secondary to chemotherapeutic agents has been minimized and almost eliminated by the policy of performing vascular access shunts for prolonged intravenous therapy after malignant disease is diagnosed [S]. A loop fistula from the saphenous vein to the superficial femoral artery is the procedure of choice in young children. Thomas shunts are used when a large volume of medication, blood, and blood products is needed, as in bone marrow transplantation patients. Results

The results of the severe extravasation injuries were uniformly poor, with attendant morbidity. (Table III.) In eight of the thirty-one patients the extravasation injury was worse than the condition that originally brought them to the hospital; most of these patients were in the middle age group range

The American Journal of Surgery

Intravenous

TABLE IV

Extravasation

Injuries

Physicochemical Properties of Some Causative Agents No. of Patients

Product Osmotically active solutions and cations 30% urea, 10% dextrose intravenous solution Calcium gluconate Potassium chloride (KCI) Calcium chloride (CaCl*) Calcium gluceptate Renografin-60 (diatrizoate meglumine and diatrizoate sodium injection USP)

mEq/ml

mOsm/l

5.5-7.0

0.16

5.0

5,000

5 6 3 1 1

448.0 74.6 147.0 490.43 809.13

6.0-7.0 4.0-8.0 6.0-7.5 6.0-7.0 6.0-7.6

-

0.446 2.0 1.36 0.897 0.75

669.60 4,000 2,040 1,345 750

190.0

3.0-4.5

-

0.211

422

317.29 333.0

3.2-4.5 2.5-3.5

8.6 5.5

0.0315 0.003

580.0 455.44

3.8-6.5 a.5

a.2 3.76 4.83 5.6

0.00172 0.0052

2 2

284.74 480.9

6.2-6.9 2.0-3.0

0.0176 0.21

17.6 623

1

264.33

10.0-11.0

3.4 3.3 7.7 9.5 -

0.9458

945.8

Cytoxic agents Adriamycin Methotrexate Sodium salt

2.5%

pKa

60.1

Aramine Epinephrine bitartrate

Sodium thiopentol (pentathol)

PR

1

Vasopressors Dopamine

Others Diazepam (Valium) Tetracycline HCI

MW

63 6 3.44 5.2

Note: MW = molecular weight.

and had been admitted to the hospital for elective surgery. Extravasation injuries in the extremities of elderly patients resulted in significant pain, limitation of motion, and decreased function, as demonstrated by a reduction in grip and pinch strength, a decreased range of motion, and difficulty in performing manipulative tasks. Five patients with significant soft tissue slough in the upper extremities developed sympathetic dystrophy syndromes. In three of these patients, the hand remained functionless, with fixed flexion contractures of all metatarsophalangeal and proximal interphalangeal joints and chronic dorsal edema. All of the patients with upper extremity lesions retained considerable joint stiffness. Eleven of the eighteen patients with soft tissue loss on the dorsum of the hand sustained extensor tendon loss. Amputation was required in two patients with arterial compromise and also would have been required in two other patients who died. All of the surviving patients in this series required operative procedures, with an average of 3.5 operations required in each patient. Most of the operations were debridement procedures and split thickness skin grafts. The extravasation injury prolonged hospitalization an average of twenty-three days, not

Volume 137, April 1979

including additional tive procedures.

hospitalization

for reconstruc-

Comments

Mechanisms of Extravasation Necrosis. The following pathophysiologic classification is useful in evaluating and treating intravenous extravasation wounds. On a cellular level, five possible mechanisms should be considered: osmotic damage, ischemia secondary to impaired circulation, direct cellular toxicity, mechanical compression, and infection. The osmotically active substances include urea and hypertonic solutions containing cations such as calcium and potassium in ionized form. When injected as a bolus into the interstitial subcutaneous space, hypertonic solutions cause osmotic imbalance across the cell membrane. The cellular transport mechanisms are disrupted, and cell death results from intracellular fluid imbibition. In contrast, urea [ 71 is a nonmetabolic nonelectrolyte that draws water from the cells, resulting in intracellular dehydration. Other important variables are the pKa (acid dissociation constant), pH of the solution, and the percentage diluent. Table IV lists the physiochemical properties of these potentially dangerous parenteral

503

Upton, Mulliken, and Murray

Figure 2. Three days after extravasation of epinephrine and Aramine during a cardiac resuscitation. The injury occurred before release of a tournfquet placed at the upper humeral level during a cut-down procedure. If the patient had not died of cardiopulmonary compllcatlons four weeks later, amputation above the elbow would have been indicated.

solutions, including pH, pKa, molecular weight, milliequivalents and osmolalities. The normal serum osmolality of 280 milliosmoles is well below the high concentration of these solutions. If calcium extravasation is recognized within 60 minutes, studies in experimental animal models indicate that full thickness damage may be reversed by clysis with sodium chloride plus hyaluronidase (150 units/l,000 cc concentration) at ten times the volume of the extravasate [8]. Unfortunately, most of these injuries are not recognized within 60 minutes. The practical clinical value of clysis with more dilute physiologic solutions or with direct instillation of steroids has not been documented in humans. Agents that cause ischemic necrosis include vasopressors and certain cation solutions. Extravasation of alpha-adrenergic stimulators such as aramine, dopamine, and epinephrine cause constriction of smooth muscle around capillaries and ischemic tissue necrosis. The duration of extravasation is more important than the concentration of vasopressor administered. Although cations such as potassium and calcium are not alpha-adrenergic drugs, they may cause ischemic necrosis by prolonged depolarization and contraction of pre- and postcapillary smooth muscle sphincters. [9]. The problem of skin necrosis secondary to vaso-

504

pressor infiltration has been well documented since the early use of Levophed” for circulatory support [IO-251. Alpha blocking agents such as phentolamine (Regitine”) and piperoxan (Benodine? are effective if the injury is recognized early. Local infiltration with Regitine is standard practice for early vasopressor infiltration [ 121. Direct cellular toxicity by extravasated agents is another possible mechanism for cell death. Adriamycin is incorporated into the cell nucleus, where it acts to inhibit DNA replication. Methotrexate, a folate antagonist, interrupts purine synthesis by binding to folate reductase, which probably accounts for its cellular toxicity with extravasation. There is some evidence that the extent of tissue necrosis may be related to the concentration of the cytotoxic drug delivered to the subcutaneous level [3,16]. Until further documentation is provided, clysis in an effort to dilute the drug is not recommended. Diazepam (Valium@) and tetracycline are both clinically irritating when extravasated and painful when injected intramuscularly. The irritation may be caused by the vehicle rather than the active drug. Pentathol, an alkaline barbiturate, may exert its necrosing effect by localized intimal damage and subsequent small vessel thrombosis. Mechanical compression of tissues secondary to

The American Journal of SurgerY

Intravenous Extravasation

Figure 3. A, three wee&s after thiopentoi extravasation caused by multiple venopuncture attempts. Radial pulse was absent preoperative/y secondary to an arlerjai line in infancy. The patient also had a history of Raynaud’s phenomena. B, six weeks after the iniury full demarcation had occurred and amputation was necessary.

intravenous extravasation is usually the result of administration with a mechanical infusion pump. Increased extracellular hydrostatic pressure causes a vicious cycle of increased interstitial pressure, venous compression, and eventual arterial compromise. Injection of fluid into a close space during duress, such as cardiac resuscitation, may also initiate such a sequence of events. Bacterial colonization is an additional factor accounting for the extent and depth of tissue loss. The organisms that normally colonize hair follicles at lo2 bacteria/gram of tissue may proliferate in the subeschar space to levels greater than lo5 organisms/ gram of tissue, which, by definition, constitutes invasive wound sepsis [5]. An open wound is also an obvious portal of entry. Preuention. The following guidelines for preventing intravenous extravasation injuries are recommended: (1) large central veins should be used during resuscitative efforts and lower extremity infusion sites particularly avoided in elderly people with preexisting vascular disease; (2) multiple perforations of the same vein and repeated use of the same vein for infusion should be avoided; (3) long,

Volume 137, April 1979

Injuries

Figure 4. A, indolent foot ulcer 140 days affer extravasatkm of 75 cc of Renografin-60 contrast dye during a pHebogram. B, three weeks later, after aggressive debridement and skin grafting.

smooth-tipped polyethylene catheters shall be used instead of sharp-tipped metal needles, especially at joint levels such as the antecubital, cubital and wrist flexion creases; (4) infusion under any pressure should be avoided, especially during resuscitations; (5) phlebotomy sites should be watched carefully in infants receiving medication through infusion pumps; (6) chemotherapy should be administered by experienced personnel with maximal dilution of the drug; (7) vascular access shunts, as for dialysis patients, should be considered for administration of cytotoxic agents; (8) all venipuncture sites should be carefully monitored during prolonged anesthesia and resuscitations; (9) any tourniquet effect cephalad to the point of infiltration should be avoided; (10) alternative intravenous sites should be considered before intravenous lines are placed directly over tendons, nerves or vessels, such as the radial artery in the wrist or the extensor tendons in the dorsum of the hand; and (11) unnecessary camouflage of the extremity and the site of intravenous administration with dressings and armboards should be avoided. Acknowledgment: We thank Shabir Z. Masih, PhD, Massachusetts School of Pharmacy, for providing qualitative analysis of the causative agents noted in this study.

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References 1. Wolfort FG, Cochran RC, Filtzer H: Immediate interossei decompression following crush injury of the hand. Arch Surg 106: 826, 1973. 2. Rudolph R, Stein RS, Pattillo RA: Skin ulcers due to adriiycin. Cancer 38: 1087,.1976. 3. Bowers, DG, Lynch, JB: Adriamycin extravasation. Plast Recons& Surg 61: 86, 1978. 4. Elias RM, Fritsch P, Epstein EH: Staphylococcal scalded skin syndrome: clinical features, pathogenesis and recent microbiological and biochemical developments. Arch Derm 13: 207, 1977. 5. Krizek TJ, Robson MC: Evolution of quantitative bacteriology in wound management. Am J Surg 130: 579, 1975. 6. Levey RH, Sallan S, Weinstein H, Jaffe N: Surgical techniques for vascular access for chemotherapy in infants and children. Ped Surg 1978, in press. 7. deStefano GA, Kahl JB, Hasfajani M, Sakler BR: Impending gangrene of hand from concentrated urea-sugar solution. Case report. Plast Reconstr Surg 44: 193, 1969. 8. Hekler FR, McGraw JB: Calcium-related cutaneous necrosis. Surg Forum 27: 553, 1976. 9. Goodman LS, Gilman A: The Pharmacologic Basis of Therapeutics, fourth edition. New York, MacMillan, 1970. 10. Nickerson M, Dresel PE: Adrenergic drugs and their antagonists. Postgrad Med 24z.246, 1958. 11. Fleckenstein A: A quantitative study of antagonists of adrenaline on the vessels of the rabbits ear. Br J Pharmacol7: 553, 1952. 12. Close AS: Phentolamine hydrochloride in prevention of cutaneous necrosis due to levarterenol. JAMA 170: 1916, 1959. 13. Pelner L, Waldman S, Rhoades MG: The problem of levarterenol (levophed) extravasation. An experimental study. Am J Med Sci 236: 755, 1958. 14. Close AS, Frackelton WH, Kory RC: Cutaneous necrosis due to norepinephrine. II. Mechanism and prevention. C/in Res Proc 4: 241, 1956. 15. Hessov I, Bojsen-Moller M: Experimental influsion thrombophlebitis. Importance of the infusion rate. Eur J lntesive Cafe Med2: 103.1976. 16. Wang JJ, Cartes E, Sinks LF, Holland JT: Therapeutic effect and toxicity of adriamycin in patients with neoplastic disease. Cancer 28: 637, 1971. 17. Donaldson SS, Glick JM, Wilbur JR: Adriamycin activating a recall phenomenon after radiation therapy. Ann intern Med 81: 407, 1974. 18. Etcubanas E, Wilbur JR: Uncommon side effects of adriamycin [letter]. Cancer Chenwther Rep 58: 757, 1974. 19. Yosowitz P, Ekland DA, Shaw RC, Parsons RW: Peripheral intravenous infiltration necrosis. Ann Surg 182: 553, 1975. 20. Enger E. Jacobsson B, Sorensen, SE: Tissue toxicity of intravenous solutions. A phlebographic and experimental study. Acta Paediafr Stand 65: 248, 1976. 21. Borgstrom S, Gelin LE. Zederfeldt B: The formation of vein thrombi following tissue injury. An experimental study in rabbits. Acta Chir Scan [Suppl] 247: 1. 1959. 22. Carter JFB: Reduction in thrombophlebitis by limiting duration of intravenous infusions. Lancet 2: 20, 1951. 23. Fonkalsrud EW: Neutralization of IV fluids. N Eng/ J Med 26, 1969. 24. Fonkalsrud EW, Murphy J, Smith FG: Effect of pH in glucose infusions on development of thrombophlebitis. J Surg Res 8: 1968. 25. Hessov I, Bojsen-Moller M: experimental infusion thrombophlebitis. Importance of the pH of glucose solutions. Eur J lntesive Care Med 2: 97, 1976. 26. Kauste 0, Rantakallio P: The role of acidity in local complications following intravenous glucose administration. Ann Paediatr Fennia 8: 119, 1962. 27. Hessov I, Allen J. Arendt K, Gravholt L: Infusion thrombophlebitis in a surgical department. Acta Chir Stand 143: 151,

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Discussion John J. Byrne (Boston, MA): These cases represent a type of needle-induced iatrogenic hand injuries. The mechanism may be infection, chemical necrosis, or ischemia due to vasoconstriction, vascular injury, or a fascial compartment syndrome. Prevention requires an awareness of the problem, with careful emphasis on antiseptic precautions and anatomic needle placement. Prompt attention to patients’ complaints will permit early diagnosis and treatment. B. Cannon (Boston, MA): This type of injury is similar to electrical burns because both involve the deeper tissues and thus pose the same difficulties in treatment. Because the tissues involved are deep, debridement is more difficult and unpredictable because the viability of the involved tissues is uncertain. Most of the patients in this study were children or elderly patients, which raises the question of whether this distribution is a result of the agents used or of the increased susceptibility of such patients to complications. Perhaps Dr. Upton would comment on the difference in the use of intravenous infusions in pediatric and adult patients and recommend a method of properly inserting the needle or the intravenous line. Joseph Upton (closing): In response to Dr. Cannon’s question, the major difference in the use of intravenous infusions is one of technique. At the Children’s Hospital entire extremities are covered with dressings and splints designed to secure intravenous lines and many times the children, especially the neonates, are so severely ill that they cannot even cry. In addition, they may be intubated. The major point of prevention is informing nurses about the potential hazards of intravenous lines. In children the problem with infiltration of cytotoxic agents has been almost eliminated by the use of vascular access shunts. As soon as the diagnosis had been made, usually by bone marrow aspiration, a shunt procedure is performed. A superficial femoral vein to femoral artery loop fistula has been the procedure of choice. When large volumes of blood, blood products, and cytotoxic agents are needed, as in a bone marrow transplantation, a Thomas shunt is usually used. Dr. Ray Levey has used these access shunts in more than 100 patients at the Children’s Hospital, but this is not standard practice at the Peter Bent Brigham Hospital now. The American Journal of Surgery