Transcutaneous gases determination in diabetic critical limb ischemia

TTranscutaneous oxygen tension (tcpo2) quantifies oxygen delivery through skin capillaries as a function of two main physiological variables, the effective rate of skin blood flow and skin resistance to oxygen permeation, represented mainly by stratum-corneum permeability (1). Tcpo2 is an accepted measure of nutritive skin perfusion (1) and predicts the therapeutic outcome in critical limb ischemia (CLI) (2), a serious complication of type 2 diabetes, a disease characterized by the coexistence of macro- and microvascular alterations (3). Transcutaneous carbon dioxide tension (tcpco2), another tensiometric parameter, is sensitive to severe limb ischemia (4) and correlates closely with HCO−3 depletion, H+ accumulation, and acidotic milieu (5). Thus, tcpco2, by providing an indication of the local acid-base balance, might improve the clinical management of patients on CLI, but its prognostic potential in that context is unknown. We addressed this issue in 31 critically ischemic limbs (n = 26 type 2 diabetic patients, n = 5 Fontaine’s stage III, n = 21 Fontaine’s stage IV) on iloprost treatment (6-h intavenous administration, 1–2 ng · kg−1 · min−1 daily for 4 weeks) using a drug that is useful for treating CLI not responsive to surgery (6). Iloprost, an analog of epoprostenol (prostacyclin, a potent but short-lived endothelial-derived prostanoid), mimics the pharmacodynamic properties of this compound, namely inhibition of platelet aggregation, vasodilatation, and, as yet ill-defined, cytoprotection (7). Infusion rates were titrated in each individual to reach the maximum tolerated dose without hypotension, tachycardia, and other common side effects (facial flushing, headache, nausea, vomiting, abdominal cramping, and diarrhea). Outcome variable was pain relief evaluated by a visual analog scale (1, no pain; 10, intolerable pain). Success (pain relief of >75% from baseline) was obtained in 16 limbs (52%) and failure in 15 limbs (48%). No patient needed surgery or amputation during that short-term study interval. Supine tcpo2 and tcpco2 were bilaterally recorded on preheated (44°C) dorsal skin between the first and second metatarsal. Response to iloprost (either success or failure) was stratified by tcpo2 and tcpco2 tertiles, and likelihood ratios (LRs) quantified the predicting power for success (percentage of successes divided by percentage of failures) or failure (percentage of failures divided by percentage of successes) of those two tensiometric parameters (8). LRs are diagnostic statistics that quantify the increased likelihood of an event according to different results of the diagnostic test under evaluation (8). Tertile cutoffs rather than threshold values derived from established literature sources were used because there is no consensus on the definition of normal tcpco2 that is valid for diagnostic and prognostic use. Iloprost failed in 10 limbs and succeeded in 1 limb in the upper tcpco2 tertile (cutoff 53 mmHg, 7.07 kPa; LR 10.7) (Table 1). Corresponding data for the bottom tcpo2 tertile (cutoff 1 mmHg, 0.13 kPa; LR 3.3) were 10 vs. 3, respectively (Table 2). All limbs in the upper tcpo2 tertile (cutoff 23 mmHg, 3.07 kPa; LR 17.8) (Table 2) responded to the drug in contrast to only 8 of 10 in the bottom tcpco2 tertile (cutoff 40 mmHg, 5.33 kPa; LR 3.8) (Table 1). Thus, the upper end of tcpco2 values predicted failure to iloprost treatment, and LR analysis confirmed that conclusion. In fact, the further LRs are from 1, the stronger their clinical impact, and when >10 (or <0.1), they should influence therapeutic and diagnostic attitudes (8). Furthermore, pretreatment supine tcpco2 >53 mmHg (7.07 kPa) predicted treatment failure threefold more efficiently (LR 10.7 vs. 3.3) than supine tcpo2 <1 mmHg (0.133 kPa), an established prognostic marker for limb salvage procedures (2), particularly at those tensions too low to be detectable by the sensor system. Conversely, therapeutic success was 17.8-fold more likely when pretreatment tcpo2 was >23 mmHg (3.07 kPa), which, according to available nomograms (8), corresponds to a 0.95 posttest probability (i.e., close to the certainty of success). Thus, combined use of tcpco2 and tcpo2 allows more precise prognostic stratification and therefore more rational treatment strategies in diabetic patients with CLI. However, this conclusion awaits further support from studies carried out in samples larger than the present one. Follow-ups longer than our 4-week interval are also needed to evaluate whether elevated tcpco2 predicts with similar efficiencies clinical end points more significant than pain relief, such as limb amputation.