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CLINICAL STATEMENTS AND GUIDELINES Circulation. 2024;149:e1313–e1410. DOI: 10.1161/CIR.0000000000001251 June 11, 2024 e1371 in duration, the benefits of thrombolysis are minimal, and attempts at revascularization using other techniques are generally necessary.36,38 3 Additional evaluation and consideration before revascularization may be warranted in patients with ALI associated with or induced by systemic proinflammatory and prothrombotic states. For example, the development of ALI as a complication of cancer chemotherapy has been described among patients undergoing treatment for different primary malignancies with regimens including platinum-based agents.8–11 In recent years, case reports of arterial thrombotic events associated with use of tyrosine kinase inhibitors have been reported.12 During the coronavirus disease-2019 (COVID-19) pandemic, dozens of case reports and case series described the development of ALI among patients infected with SARS-CoV-2, including among patients with severe multiorgan failure.6,7,13,14 In these complex cases of ALI associated with underlying systemic illness or its treatment, additional consideration may include further noninvasive imaging (ie, duplex ultrasound, CTA, MRA), evaluation of clinical stability and comorbidities, and multidisciplinary discussion in determining the treatment approach (medical therapy with anticoagulation and monitoring rather than initial revascularization). During this evaluation, such patients are treated with unfractionated heparin, in the absence of contraindications (see Section 11.2.3, “Anticoagulation for ALI”). 4. For patients with category III ALI (irreversible ischemia), amputation of nonviable tissue should be performed as the index procedure rather than revascularization. The risks associated with revascularization (ie, procedural complications) outweigh the potential benefit if the extremity is already insensate or immobile because of prolonged ischemia. In addition, in this setting, reperfusion and circulation of ischemic metabolites can result in multiorgan failure and cardiovascular collapse.43 11.2.2 Adjunctive Therapies to Minimize Tissue Loss in ALI Recommendations for Adjunctive Therapies to Minimize Tissue Loss in ALI Referenced studies that support the recommendations are summarized in the Online Data Supplement. 1 C-EO 1 Patients with ALI should be monitored and treated for compartment syndrome with fasciotomy after revascularization (endovascular or surgical, including catheter-directed thrombolysis) to prevent the sequelae of reperfusion injury and need for amputation. 2a B-NR 2 In patients with ALI with a threatened but salvageable limb (ie, category IIa or IIb), prophylactic fasciotomy is reasonable based on the clinical findings.1,2 2a C-EO 3 In patients with ALI and prolonged ischemia in whom revascularization (endovascular or surgical, including catheter-directed thrombolysis) is performed, concurrent and early amputation can be beneficial to avoid the morbidity of reperfusion. Synopsis Patients presenting with ALI experience elevated rates of morbidity, mortality, and limb loss.3,4 Timely revascularization is the goal but, even with this, poor outcomes may be unavoidable. Adjuncts to limb revascularization, including fasciotomy for compartment syndrome and amputation, may be necessary to minimize tissue loss and preserve maximal limb function. Unlike patients in whom traumatic limb injury has occurred, elevated compartment pressures are generally not present at the time of initial presentation of ALI. In ALI, with partial or complete revascularization, reperfusion injury can occur. The mechanism is attributed to the release of oxygen-free radicals that create a leaky capillary process, resulting in elevated compartment pressures in the limb. Compartment syndrome is more likely to occur with prolonged periods of ischemia and more severe ischemia. Short periods of ischemia may be poorly tolerated in the patient with no preexisting PAD, although longer periods of ischemia may result in less cellular injury for the patient with chronic PAD and preexisting collateralization.5–7 The diagnosis of compartment syndrome is based on the history (including the duration of ischemia) and associated clinical findings (eg, elevated serum creatine kinase) but, in certain circumstances, may be confirmed with the measurement of elevated compartment pressures. Although compartment syndrome can also occur in the thigh, the lower leg is by far the most common site.7 A high clinical suspicion is necessary to permit early diagnosis of compartment syndrome so that timely decompression with surgical fasciotomy can interrupt the progression of ischemia leading to tissue necrosis. Recommendation-Specific Supportive Text 1 The lower extremity muscles are at risk for reper- fusion injury in patients with ALI.1 Reperfusion to ischemic muscles can cause cellular edema within fascial compartments, resulting in increased compartment pressure and the development of clinical compartment syndrome. Monitoring for compartment syndrome is an important component of care for patients with ALI. For patients with clinical evidence of compartment syndrome (ie, based on physical examination, elevated serum creatine kinase, or both), immediate fasciotomy is indicated. Prompt action to measure compartment pressures Recommendations for Adjunctive Therapies to Minimize Tissue Loss in ALI (Continued) COR LOE Recommendations COR LOE Recommendations Downloaded from http://ahajournals.org by on October 7, 2026