The definition of CLI has evolved over time. It has been classically defined as greater than 2 weeks of extremity rest pain, ulcers, or extremity gangrene, secondary to objectively proven peripheral artery disease. In its most extreme case, CLI can lead to limb loss [1, 2].

Several criteria are often used for objective evidence of CLI, but most commonly involve: (a) ankle-brachial index (ABI) of 0.4 or less, (b) ankle systolic pressure of 50 mmHg or less, (c) toe systolic pressure of 30 mmHg or less, (d) toe-brachial index (TBI) of 0.25 or less, and (e) reduced supine forefoot transcutaneous oxygen pressure (TcPO2) less than 30 mmHg [3, 4]. Although not an exact definition, CLI would be seen as corresponding with stages III and IV of Fontaine Classification and categories 4 through 6 of the Rutherford classification system [5, 6] (see Table 2.1).

While the Fontaine and Rutherford classification systems originally were implemented to categorize peripheral arterial disease by symptoms several decades ago, objective criteria were adapted as technology has developed and several consensus documents have then evolved the definition of CLI [7].

The first consensus document was the Second European Meeting Consensus Document on CLI (1991) that used two definitions for CLI based on clinical use and on research use [4] as written below:

There has been some debate on the value of ankle pressures . However these definitions have been generally agreed upon as the threshold to be used.

The next large summary consensus was the Trans-Atlantic Inter-Society Consensus (TASC) Document on Management of Peripheral Arterial Disease (2000) that did continue the method of having a clinical definition, as well as a research definition. It also changed the thresholds for some of the objective criteria [8]:

Here, there is an emphasis on CLI being defined by symptoms and showing objective-proven arterial occlusive disease. The thresholds for ankle pressure were raised, possibly to answer some of the critics of the 1991 European Consensus Document. However, the toe pressure and TcPO2 pressure thresholds were also raised.

The ACC/AHA created practice guidelines in 2005 for management of patients with peripheral artery disease and also addressed the definition of CLI using some of the other consensus statements [9]. It uses the TASC clinical definition as above and points out that most vascular clinicians would define CLI as those patients in whom the untreated natural history would lead to a major limb loss within 6 months [9].

The most recent consensus statement is the TASC Document that was updated (TASC II 2007) that simplified the definition: “The term critical limb ischemia should be used for all patients with chronic ischemic rest pain, ulcers or gangrene attributable to objectively proven arterial occlusive disease. The term CLI implies chronicity and is to be distinguished from acute limb ischemia” [3]. It also stresses that ischemic rest pain will most often occur with ankle pressures <50 mmHg and toe pressures <30 mmHg but that in situations where healing is needed (if a venous or traumatic ulcer is not healing well due to poor arterial flow), often ankle pressures less than 70 mmHg and toe pressures less than 50 mmHg are insufficient [3]. There is not complete consensus as to the objective vascular parameters to be used for CLI, but the thresholds we have mentioned are the most commonly used in various clinical practices, as well as for various research articles and publications.

CLI is most often caused by, and associated with, obstructive atherosclerotic arterial disease. While most risk factor modification, research, and focus are on this disease process, it is important to note that since CLI results from the imbalance between supply of nutrients and metabolic demand in distal tissues, there are other causes that can result in CLI. Other causes can include atheroembolic/thromboembolic disease, thrombosis resulting from hypercoagulable states, vasculitides, thromboangiitis obliterans, cystic adventitial disease, Buerger’s disease, thoracic outlet syndrome, popliteal entrapment syndrome, trauma, and more [9, 10]. There are also multiple risk factors to CLI as well as contributing factors to the acceleration of the disease process that will be addressed elsewhere.

Peripheral arterial occlusive disease has been well studied over the last several decades with most research dealing with symptomatic disease , including intermittent claudication through the extreme of limb loss. It has been noted that there is a prevalence of 8–10 million Americans who suffer from arterial occlusive disease [3]. While the reported prevalence of peripheral arterial disease (PAD ) may depend on the particular population studied, and the modality used to diagnose it (subjective and objective criteria), if one uses PAD to be defined by an ankle-brachial index of <0.90, then it may likely be present in up to 4–10 % of patients in the USA and Europe [11–13] and involving a prevalence of an estimated 27 million people in those same areas [14].

There is widespread data about the incidence and prevalence of PAD as an entity; however, there is limited data regarding chronic critical limb ischemia. It is difficult to obtain specific epidemiologic data for CLI for several reasons [7]. First, the identification of CLI is more difficult than identifying some other conditions (like PAD as defined by ABI <0.90). As stated above, a general definition that most clinicians use is by attributing rest pain, ulcers, or extremity gangrene to a peripheral arterial occlusive disease, and that lasts longer than 2 weeks. This requires a level of proficiency and diagnostic assessments that are not often readily available in large epidemiological studies [7].

Secondly, as noted, the definition of CLI has evolved over time. There is a heterogeneity of many studies using different definitions and often without the objective parameters to define that CLI has been published. There are often major differences between the various studies that can make the data inconsistent. Lastly, the actual numerical epidemiological data that is usually used and cited is often inferred from other markers, such as the incidence of amputations (which assumes that a quarter of CLI patients undergo this procedure). Data is often presented from assumptions of the natural history of PAD (i.e., perhaps the estimate that 5–10 % of patients with either asymptomatic PAD or claudication will go on to become CLI at 5 years time) [3, 7].