The authors studied whether skin perfusion pressure (SPP) measurements can be used to accurately predict wound healing in critical limb ischemia (CLI) and to select peripheral arterial reconstructive procedures. Methods. Forty-seven patients (33 men and 14 women, age 36–83 years) with 69 ischemic limbs with foot ulcers or gangrene were studied retrospectively. Skin perfusion pressure was compared to the treatment outcomes (ulcers healed and ulcers that failed to heal). As a diagnostic test for CLI, the sensitivity, specificity, and the positive and the negative predictive values (PPV, NPV) of SPP measurement were calculated; the data was then analyzed by the receiver operation characteristic (ROC) curve. Results. According to the ROC curve, the best SPP measurement performance was at 35 mmHg. Conclusion. Wound healing at the appropriate amputation level must be predicted to minimize invasive debridement. Skin perfusion pressure measurement is useful for predicting wound healing in the presence of CLI. Skin perfusion pressure ≥ 35 mmHg is requisite for wound healing; at SPP < 35 mmHg, peripheral arterial reconstruction is necessary before debridement.

       Foot ulcers or gangrene with associated peripheral arterial disease (PAD) are a challenge to treat. Amputation of the toes and metatarsal bones is better tolerated than more extensive amputation because patients who undergo the former can be rehabilitated easily and can return to a good quality of life. In addition, the bony structures of the foot may be remodeled in such a way to prevent further injury.¹ The evaluation of blood flow in the lower extremities is crucial in managing foot ulcers or gangrene with PAD. The goal of achieving the lowest possible level of amputation and minimal invasive debridement is maximal preservation of functionality and mobility. However, if the amputation is selected at a more distal level where blood supply may be inadequate for healing, it may lead to further tissue necrosis and additional surgery. Repeated operations may subject patients to prolonged treatment and long-term hospitalization. Therefore, when blood flow is insufficient, surgical debridement of necrotic tissue in foot ulcers with PAD should be postponed until after the restoration of adequate blood flow to the skin.² To achieve minimal invasive debridement, adequate blood flow must be supplied at the amputation level. It is essential to evaluate blood flow that promotes wound healing by only local management or by some peripheral arterial reconstruction. Several tests including ankle brachial index (ABI), toe pressure (TP), and transcutaneous oxygen tension (TcPO₂),^3–9 have been devised to provide objective data to determine the most distal level where wound healing is efficient. Although not one test has gained universal acceptance, the authors use the laser Doppler skin perfusion pressure (LD-SPP)^10–12 method. Skin perfusion pressure has been shown to be a reliable predictor of wound healing.^10–18 The authors measured SPP at the proximal margin of foot ulcers (not in the wound bed) in patients referred to the Wound Treatment Center at Shin-Suma General Hospital (Kobe, Japan) for the treatment of intractable foot ulcers, and compared it with the outcomes of treatment (healed or failed to heal). Skin perfusion pressure was compared before and after peripheral arterial reconstruction. The effect of SPP elevation on wound healing was also evaluated.

Materials and Methods
       Patients. From January 2003 to September 2004, 69 foot ulcers or gangrene were studied in 47 patients (33 men and 14 women, 36- to 83-years-old; mean 69.5 years) referred to the Wound Treatment Center at Shin-Suma General Hospital (Kobe, Japan). Comorbidities were diabetes mellitus (27 patients, 55.3%) and ongoing renal dialysis (17, 36.2%). All study participants gave written informed consent.

Figure 1.

       Measurement of laser Doppler skin perfusion pressure. Testing was carried out at initial diagnosis with a Laserdopp PV-2000 (Kaneka, Osaka, Japan). The laser Doppler flow sensor was secured within the bladder of a blood pressure cuff equipped with a transparent polyvinyl chloride window for measuring microcirculatory perfusion during cuff inflation and deflation. Three cuffs of different sizes were used for the toe, ankle, and leg. Patients were placed in a supine position, kept still for 5 minutes, and then their brachial blood pressure was measured. The appropriate cuff was applied to the proximal margin of the ulcer, inflated to 20 mmHg above the brachial systolic pressure, and a stable laser Doppler output value near zero (< 0.1 volume%) was reached before deflating. The cuff was deflated first in 10 mmHg-stepwise decrements every 5 seconds to a pressure of 50 mmHg, and then in 5-mmHg decrements every 15 seconds until the laser Doppler output increased for 2 consecutive pressure values. The pressure at which this first occurred was considered as the SPP value (Figure 1).
       Foot ulcers that did not heal within 12 weeks after debridement or minor amputation or that required peripheral arterial reconstruction or more proximal amputation were evaluated as “failed to heal.” Those that demonstrated complete wound closure without additional surgery were evaluated as “healed.”

Results

Figures 2 and 3.

       The average SPP of patients with healed wounds was 60 mmHg. The average SPP for patients with unhealed wounds was 31 mmHg. The data, analyzed to determine the optimal cutoff level for SPP, showed that SPP levels below the threshold gave a positive result and were predictive of healing failure (true positive and false positive), and SPP levels above the threshold gave a negative result, and were predictive of healing success (true negative and false negative). Skin perfusion pressures predictive of wound healing are shown in Figure 2. The sensitivity, specificity, and the positive and the negative predictive value of the test results were calculated (Table 1). An analysis of the graphic representation of these data showed that the optimal SPP level was 35 mmHg (ROC curve; Figure 3).
       Next, comparison of each SPP value before and after 11 distal bypass surgeries (Figure 4) showed that average SPP value was 20 mmHg before surgery and 60 mmHg after surgery. Eight of 11 limbs showed a marked increase in SPP that prompted wound healing after successful patency. Distal bypass surgery failed in 2 of the 3 limbs that did not heal and required major amputation because the SPP did not change. The remaining patient died of cardiac infarction postoperatively.

Table 1.

Discussion
       Selection of the proper amputation level is crucial not only to preserve the maximal length of the viable extremity, but to minimize morbidity and mortality. When overly distal amputation is selected, the blood supply may be inadequate for wound healing and additional surgery may be required. Repeated amputation, which may cause greater morbidity or mortality, should be avoided. Overly proximal amputation without prosthesis may lead to difficulty in ambulation.¹³

Figure 4.

       Selection of the amputation level where the blood supply is sufficient for wound healing is one of the most difficult problems when treating patients with CLI. Although several noninvasive measurements are available for predicting wound healing after debridement or amputation, not one has gained widespread acceptance. The ankle/brachial systolic pressure index (ABI) is inexpensive and easy to obtain for routine inspection. However, the ABI is difficult to apply correctly in the evaluation of patients with diabetes mellitus and PAD because arterial rigidity associated with medial calcification might interfere with accurate measurement of ankle pressure.^6,10,12 Also, such measurement cannot signify isolated obstruction in 1 or even 2 of the 3 branches of the popliteal artery between the knee and the ankle, or the obstruction in more distal vessels in the foot itself.^9,12 Toe pressure (TP) measurement is not thought to be affected by arterial calcification and can signify obstruction in the distal part of the ankle. However, TP of patients with PAD is impossible to measure in the presence of ulcers, gangrene, or the loss of the toe due to previous minor amputation. Therefore, measurements of ABI and TP have limitations. Although the measurement of transcutaneous oxygen tension (TcPO²) has been suggested to be a predictor of wound healing after amputation,^4–9 it is a time-consuming procedure, is influenced by factors such as local edema and anemia, and is less reproducible than other methods.^5,8,10 Skin perfusion pressure measured by the xenon radioisotope washout technique¹⁷ is defined as the external pressure needed to stop, with the use of histamine, the microcirculatory washout of intradermal deposits of radioactive isotopes. This method has been confirmed in a well-designed prospective trial of the predictive value of SPP for amputation wound healing.¹⁵ Although SPP measured by radioisotopes can predict wound healing accurately, the technique is somewhat impractical, expensive, and time-consuming.^9,10 Laser Doppler SPP (LD-SPP) has been introduced as a simple, noninvasive method in predicting wound healing^10–12 that can achieve a 0.991 coefficient of correlation with the radioisotope washout technique,¹⁸ and is closely correlated with TP in the limbs of patients with or without diabetes.^12,16 Laser Doppler SPP is not expensive, invasive, or time-consuming in comparison to the radioisotope washout technique. The device is portable and testing can be carried out at bedside. Furthermore, the wound can be accurately evaluated on both sides (dorsal and plantar) of the amputation level. Consequently, SPP measurement can disclose isolated obstruction in 1 or even 2 of the 3 branches of the popliteal artery between the knee and the ankle. Okamoto et al¹⁹ reported that SPP is the most useful tool with respect to both sensitivity and specificity for detection of PAD.
       The threshold of effective wound healing pressure has been suggested as 30 mmHg.^10,17 The authors tentatively adopted this level; however, the specificity and the PPV were 56.4% and 73.5% for SPP > 30 mmHg. The results of minor amputation at the metatarsal and toe levels are less encouraging than those of major amputation.¹⁰ In a comparison of thresholds between 20 mmHg–60 mmHg, 35 mmHg or greater had higher specificity and PPV than 30 mmHg or greater. To avoid repeated operation, SPP > 30 mmHg is requisite for wound healing. The ROC curve indicated that the optimal SPP lies at 35 mmHg. In contrast, at a threshold of 60 mmHg, the negative predictive value (NPV) dropped to 62.8%, suggesting that peripheral arterial reconstruction may not always be necessary to facilitate an efficient wound healing process, or that a much proximal amputation level is necessary. The authors propose that when the SPP value is not ≥ 35 mmHg, any surgical debridement should be secondary to the restoration of adequate skin blood flow to minimize invasive debridement. When the SPP is ≥ 35 mmHg, surgical debridement of necrotic tissue is feasible without any peripheral arterial reconstruction.
       The change in SPP before and after distal bypass surgery showed that the value increased significantly after successful surgery (Figure 4). At elevated levels of SPP, wound healing was efficient after local therapy (minimal invasive debridement). In contrast, without an elevation in SPP, wound healing did not occur and major amputation was unavoidable. An increase in SPP is indispensable for effective wound healing. TcPO2 measurement is also useful in identifying a negative outcome; however, even in patients who undergo successful revascularization, it takes 3–4 weeks for TcPO₂ levels to rise²⁰—a phenomenon related to postoperative edema that suggests surgical debridement should be carried out 3–4 weeks after successful revascularization.²⁰ In the SPP measurements, however, increases in SPP levels were observed soon after successful revascularization. Necrotic tissue should be debrided as soon as possible after revascularization to avoid infection. Thus, SPP measurement is useful in identifying a negative outcome soon after peripheral arterial reconstruction, and can be used in the accurate evaluation of post peripheral arterial reconstruction.
       A strategy for treating critical limb ischemia using SPP is shown in Figure 5.

Figure 5.

Algorithm for management of critical limb ischemia.

       Wound healing in CLI with SPP measurement at initial diagnosis was evaluated. A treatment plan was formulated based on the SPP data. With SPP < 35 mmHg, peripheral arterial reconstruction is carried out before debridement. Where peripheral arterial reconstruction is not possible or where SPP ≥ 35 mmHg after peripheral arterial reconstruction is not attainable, there is no choice but to select a higher level of amputation. Debridement can be done at an amputation level where the SPP value is ≥ 35 mmHg. After preparing the wound bed including debridement, the wound is closed primarily (eg, minor amputation) or secondarily (eg, guillotine amputation).

Conclusion
       This study demonstrates that SPP measurement is useful in accurately planning minimal invasive amputation and for predicting successful wound healing in CLI.