Vascular Injury Secondary to Drug Abuse

Pathophysiology

IADI results in injury to the arteries, arterioles, capillaries, and venules. Arterial spasm, embolization of particulate matter, alternations in pH with drug crystallization, platelet aggregation, thromboxane release, and sympathetic-mediated vasospasm have all been proposed to account for ischemic changes. The initial injury appears to affect the venules as the drug and particulate matter pass through the arteriolar and capillary system, then injure venous endothelium, leading to venospasm and venous thrombosis ( Figure 1 ). The venous injury results in outflow obstruction and slowed perfusion, causing stagnation in the arterioles. The result is secondary arteriolar endothelial injury, intimal disruption, and local thrombosis. In addition, outflow obstruction from venous thrombosis increases capillary pressure, leading to increased interstitial pressure and impaired tissue perfusion. The arterial insufficiency, venous injury, and loss of perfusion combine to result in tissue ischemia.

Secondary arterial injury results from chemical arteritis (inflammation in response to compounds present in the injected substance) and direct endothelial cytotoxic effects. Direct endothelial injury has been confirmed histologically, with vessel wall necrosis occurring within 24 hours after injection. These examinations have found the arterial wall to be amorphous and weakly acidophilic, with destruction of cellular architecture and nuclei. The intima has no viable endothelium, although arteriolar thrombosis might not be apparent for 48 to 72 hours. As the inflammatory response progresses and thrombosis develops, tissue perfusion is further reduced.

Presentation

Almost without exception, patients present with unrelenting severe pain. Following upper extremity injection, the forearm is often edematous and the hand is usually cool. The fingers are commonly mottled, cyanotic, or gangrenous, with impaired sensation and minimal motor function ( Figure 2 ). Radial and ulnar pulses are usually present, and the presence of intact pulses helps distinguish IADI from other causes of acute ischemia ( Figure 3 ). Although distal pulses are often palpable, plethysmography often fails to identify digital pulses owing to distal arterial occlusion.

Initial examination should assess the extent of ischemia and the status of motor and sensory function because the clinical signs and severity of injury correlate with the ultimate outcome and extent of tissue loss. The likelihood of permanent neurologic dysfunction of tissue loss can be more accurately determined through evaluation of the color, capillary refill, temperature, and sensory function of the affected extremity at the time of initial presentation ( Table 1 ). Patients with three or more abnormal findings are significantly more likely to develop neurologic dysfunction or tissue loss than those with one or two abnormal signs if treatment is not initiated within 48 hours of injury.

Evaluation and Diagnosis

Arterial and venous duplex scan of the affected extremity should be the initial diagnostic test. Duplex can identify the presence and extent of thrombus, identify a pseudoaneurysm, and detect an infected hematoma or abscess. Computed tomography arteriography (CTA) is rarely indicated unless duplex scan is nondiagnostic. Venography is not appropriate and can lead to further venous spasm, and arteriography is not indicated except for intraarterial thrombolytic therapy or to plan arterial revascularization.

Treatment

The fundamental goal of treatment is to prevent arterial, capillary, and venous stasis, maintain tissue perfusion, prevent thrombosis, control local inflammation, and minimize edema. This goal, in turn, is intended to prevent compartmental hypertension, systemic infection, and gangrene.

The largest experience with a defined treatment protocol comes from Los Angeles County–University of Southern California Medical Center, with its effectiveness on 69 patients reported in 1990. In that study, patients were treated with IV heparin sodium 10,000 units, followed by a continuous heparin infusion adjusted to keep the partial thromboplastin time (PTT) at 2 to 2.5 times control, dexamethasone 4 mg IV every 6 hours, and low-molecular-weight dextran (dextran-40) by IV infusion at 20 mL/hour ( Box 1 ). Narcotics were given as required for pain control, the extremity was elevated in an Osborne sling, and early active and passive range of motion were instituted. The protocol was continued for a minimum of 48 hours and continued thereafter until symptoms completely resolved or extremity function no longer improved. Débridement of nonviable or gangrenous tissue was delayed until there was demarcation to allow preservation of as much potentially viable tissue as possible.

Patients managed with this protocol with one or two abnormal findings had an excellent prognosis, regardless of the time from injury to the initiation of treatment ( Table 2 ). For patients with more than two abnormal findings, time to initiation of treatment was important. This protocol was not based on randomized clinical data and has not been compared with other management schemas. Nevertheless, early initiation was found to be effective in preventing tissue loss and permanent neurologic dysfunction in patients with more than two abnormal signs.

Other protocols have been reported seeking to control the same mediators of tissue destruction and vessel thrombosis. A protocol from the University of Texas Southwestern Medical Center from 1991 recommended initiating heparin followed by arteriography to identify arterial spasm. If arterial spasm is present, intraarterial infusion of dexamethasone and tolazoline is initiated, with follow-up arteriography. Unless flow is improved, streptokinase is infused through the catheter, and infusion of thrombolytics and vasodilators is continued for up to 72 hours. The protocol appeared to be effective but was initially reported for only three patients. Nevertheless, the concept of continued reassessment and therapy modification in response to clinical improvement seems reasonable, although the extent of tissue destruction and residual neurologic impairment is often not apparent for several days after therapy is undertaken.

Few protocols have been presented despite the availability of novel pharmacologic agents. When anticoagulants, antiplatelet agents, and steroids have not resulted in clinical improvement, anecdotal reports have found a benefit with prostaglandin inhibitors, local chemical sympathectomy, intraarterial urokinase, prostacyclin infusion, or intraarterial or systemic tissue plasminogen activator (TPA). Thrombolytic therapy may be appropriate for impending tissue loss and ischemic progression despite anticoagulation, antiplatelet, and antiinflammatory therapy. A hyperbaric oxygen protocol has been reported that requires placing the patient in a hyperbaric chamber and breathing 100% oxygen by way of a demand mask at 2.5 atmospheres absolute pressure for 90 minutes each session. Twice-daily treatments are used for 4 days, and then 10 daily treatments for a total 18 treatments. Anecdotal success with limb and neurologic preservation was reported. However, a 2002 report concluded “there are no well controlled studies that clearly demonstrate the effectiveness of any given therapy over another.”