What is critical limb ischemia?

What is Critical Limb Ischemia

Critical limb ischemia (CLI) is a chronic condition characterized by limb pain occurring at rest, ulcers, or gangrene caused by severe compromise of blood flow to the affected extremity due to objectively proven arterial occlusive disease. 1

Core Definition

CLI represents the most severe manifestation of peripheral arterial disease where resting perfusion is inadequate to sustain viability in the distal tissue bed. 1 The term specifically implies chronicity and must be distinguished from acute limb ischemia, which develops suddenly over less than 2 weeks. 1, 2

The formal definition requires all three components: 1

• Chronic ischemic rest pain, ulcers, or gangrene
• Objectively proven arterial occlusive disease
• Symptoms attributable to this arterial insufficiency

Clinical Presentation

Patients typically present with severe limb pain at rest that worsens when supine (lying in bed) and improves with limb dependency (hanging the leg down). 1 This pain commonly:

• Disturbs sleep and requires narcotic analgesia 1
• Renders patients severely disabled and often unable to walk 1
• May be accompanied by trophic skin changes or tissue loss 1

Important caveat: Diabetic patients with CLI may present with severe tissue loss but no pain due to concomitant neuropathy, making diagnosis more challenging. 1

The quality of life for patients with severe CLI can be worse than that of patients with terminal cancer. 1

Objective Hemodynamic Criteria

Patients at risk for CLI are defined by: 1

• ABI less than 0.4 in non-diabetic individuals
• Any diabetic individual with known lower extremity PAD (regardless of ABI)

For confirmed CLI with ischemic rest pain, hemodynamic studies typically show: 1

• ABI <0.40
• Ankle pressure <50 mmHg
• Toe pressure <30 mmHg
• TcPO₂ <30 mmHg

Modern Classification: Chronic Limb-Threatening Ischemia (CLTI)

The 2017 ESC guidelines introduced the term "chronic limb-threatening ischemia" (CLTI) to replace "critical limb ischemia" because: 1

• "Critical" falsely implies urgent treatment is always needed to avoid limb loss, when some patients maintain limbs for extended periods without revascularization
• The increasing predominance of diabetes (50-70% of cases) presents mostly as neuro-ischemic diabetic foot ulcers
• Amputation risk depends not only on ischemia severity but also on wound presence and infection

The WIfI classification system grades three primary factors: 1

• Wound (0-3)
• Ischemia (0-3)
• foot Infection (0-3)

Risk Factors That Increase Limb Loss

Factors that reduce microvascular blood flow: 1

• Diabetes
• Severe renal failure
• Severely decreased cardiac output (severe heart failure or shock)
• Vasospastic diseases (e.g., Raynaud's phenomenon, prolonged cold exposure)
• Smoking and tobacco use

Factors that increase microvascular blood flow demand: 1

• Infection (cellulitis, osteomyelitis)
• Skin breakdown or traumatic injury

Natural History and Prognosis

Without treatment, the natural history of CLI leads to major limb amputation within 6 months. 1 CLI is associated with: 3

• Significant morbidity and mortality
• Physical consequences including amputation
• Psychosocial consequences including depression
• Heightened risk of contralateral leg amputation after major amputation

Key Distinguishing Features from Other Conditions

CLI differs from intermittent claudication in that: 1

• Claudication causes exertional leg pain that resolves with rest
• CLI causes rest pain and inadequate resting perfusion
• CLI threatens limb viability; claudication does not

CLI differs from acute limb ischemia in that: 1, 2

• Acute limb ischemia develops suddenly (symptoms <2 weeks) with the "5 P's": pain, paralysis, paresthesia, pulselessness, and pallor
• CLI is chronic and develops gradually
• Acute limb ischemia is a vascular emergency requiring immediate intervention