Resolving the high stakes of limb salvage with skin perfusion pressure

Perfusion assessment is a cornerstone of the management of critical limb ischemia (CLI), and is recommended by contemporary guidelines to direct treatment. ¹ However, important limitations exist when applying physiologic vascular testing suitable for the evaluation of claudication (i.e. ankle–brachial index [ABI]) to assess perfusion for the patient with CLI. Indeed, the shortcomings of ankle systolic assessment for CLI have been well established.^2–4 Therefore, perfusion assessment for CLI requires unique physiologic testing sensitive to regional blood flow while remaining reliable despite arterial calcification.

Medial arterial calcification, common to patients with CLI-associated diabetes and chronic kidney disease, falsely elevates the ankle systolic blood pressure and represents the greatest limitation to non-invasive testing. Toe systolic pressure, transcutaneous oximetry (TCOM), and skin perfusion pressure (SPP) are the currently recommended tests to assess limb perfusion in CLI. ¹ However, these tests favored for CLI are inconsistently available and preference for one test over the other is not explicitly directed by current guidelines. But which of these tests might offer the most meaningful information to save a threatened limb from CLI?

Skin perfusion pressure (SPP) is a non-invasive test of regional perfusion able to assess the severity of tissue ischemia, the prognosis for ulcer healing, and as a predictor for the appropriate level of amputation.^5,6 As a measure of microperfusion at a depth 1–2 mm below the skin’s surface, SPP is unaffected by medial arterial calcification, making the measure particularly suitable among patients with complex peripheral artery disease (PAD).^6,7 SPP is defined as the minimal external pressure on the skin at which capillary blood flow is present during external cuff pressure applied immediately proximal to the local zone of flow assessment. ⁷ During stepwise reduction in external compression, the pressure at which microcirculatory flow resumes, which is assumed to represent SPP, can then be detected by one of three techniques, including radioisotope clearance, photoplethysmography, and laser Doppler. ⁸

In contemporary practice, laser Doppler SPP serves as a reasonable surrogate for toe systolic pressure when the latter is not attainable, such as in the case of transmetatarsal amputation. ⁹ SPP values above 30 mmHg,^5,6,10 and more generally above 40 mmHg,^11–13 have been proposed as a mark of adequate perfusion, above which healing is more likely. The combination of SPP > 40 mmHg and toe systolic pressure > 30 mmHg is associated with particularly high rates of healing. ¹² While SPP also correlates with TCOM, significant variability exists in the results of TCOM at low perfusion pressure.^7,8,12 So, is SPP the under-promoted answer to assessing limb perfusion in CLI?

To help understand that question, the results of several important studies have recently been published. In this edition of Vascular Medicine, Yamamoto and colleagues explore the utility of SPP in a real-world, single-center, retrospective experience of 192 Japanese patients with SPP assessment before and after 223 consecutive lower extremity bypass surgeries. ¹⁴ Patients with CLI, as confirmed by a SPP < 40 mmHg, were offered open surgical revascularization. Baseline SPP was indicated by the lower of a plantar and dorsal SPP measurement on the ipsilateral foot. The authors hypothesized that restoring a post-revascularization SPP to levels ≥ 40 mmHg might be predictive of the study’s primary endpoint of amputation-free survival (AFS). The patient population was representative of other CLI studies: the median age was 70 years, 70% were male, 68% had diabetes, 87% had Rutherford–Becker class 5 or 6 CLI, and most patients received multilevel revascularization common for CLI. The mean SPP at baseline was 20 ± 11 mmHg and rose to a mean 49 ± 18 mmHg postoperatively, corresponding to a mean increase in SPP of 28 ± 18 mmHg.

Endpoints of the analysis included AFS, limb salvage, and survival estimated out to 5 years. ¹⁴ Endpoints were analyzed among a selected population of 163 patients receiving 189 bypass surgeries for TASC C or D stenosis with confirmed postoperative graft patency. Post-revascularization SPP ≥ 40 mmHg was, in fact, not associated with improvement in any of these outcomes. Additional exploratory analysis found that an absolute increase ≥ 20 mmHg after bypass surgery was associated with improved AFS compared with those who did not achieve a similar gain in SPP. However, the rates of limb salvage and overall survival were otherwise not different based on achievement of a post-revascularization SPP ≥ 40 mmHg or a relative SPP increase of ≥ 20 mmHg. A multivariable regression analysis found a preoperative SPP < 20 mmHg and hypoalbuminemia to be predictive of a ≥ 20 mmHg increase in SPP after bypass surgery, although a validation cohort to confirm these findings was not provided. Considering these results in the context of other studies, is SPP able to accurately predict endpoints for the threatened limb?

It may depend on the endpoint. With regard to wound healing – a function of macrovascular and microvascular flow – SPP does seem predictive. Multiple studies have demonstrated that a skin perfusion pressure ≥ 40 mmHg is sufficient to heal a nearby wound.^5,6,12 The ability to substantially improve SPP, such as > 20 mmHg, may be an indication of baseline microvascular health. In that framework, post-revascularization wound blush has also been proposed as angiographic evidence of intact microvascular perfusion. ¹⁵ Indeed, wound beds with post-revascularization blush have been associated with significantly higher baseline SPP than among wound beds without blush. Despite an association of higher baseline SPP to post-procedure wound blush, which might indicate a ‘healthier’ population with less microvascular disease to start with, wound blush was a strong marker of healing among those receiving digital subtraction angiography following endovascular therapy to the limb.

For endpoints dependent upon macrovascular function, such as the likelihood of major amputation, limb salvage, and overall survival, the predictive ability of SPP is less consistent. While some studies ¹⁶ have demonstrated an association of post-procedural SPP to AFS, other studies, ¹⁵ including the present study by Yamamoto and colleagues, ¹⁴ have not. Such discrepancies reflect the challenge in predicting major amputation and AFS among a complex population with many factors influencing such outcomes. Furthermore, Yamamoto and colleagues found the relative ability to improve SPP > 20 mmHg was associated with lower AFS, whereas achieving a SPP threshold of 40 mmHg was not; that difference may indicate how SPP reflects baseline health status. Such association of SPP to macrovascular outcomes warrants further study, particularly as microvascular disease likely indicates poor general health, including a compromised nutritional status – a marker of mortality among a population with CLI. ¹⁷ Nevertheless, based on available studies, post-procedural SPP has been inconsistent as an indicator of major amputation and survival.

In the end, SPP remains a clinically relevant and objective measure of local perfusion in the setting of CLI, particularly among complex patients with calcified arteries and comorbidities that lend to microvascular disease. SPP is an important endpoint for wound healing, although its utility for limb salvage is less certain. Despite these shortcomings, guideline recommendations for ancillary microperfusion assessment are supported, especially when toe systolic pressure is suspected to be inaccurate or unavailable. SPP fills a unique niche within a cadre of tests to assess perfusion that serve as the foundation of managing patients with CLI.