TY - JOUR
AU - Amann, W
AB - Abstract Background Spinal cord stimulation (SCS) may have a place in the treatment of patients with inoperable chronic critical leg ischaemia. Methods A systematic review and meta-analysis was performed of all controlled studies comparing SCS in addition to any form of conservative treatment for inoperable chronic critical leg ischaemia. Main endpoints were limb salvage, pain relief and clinical situation. Systematic methodological appraisal and data extraction were performed by independent reviewers. Results Of the 18 reports found, nine trials, comprising 444 patients, matched the selection criteria. After pooling, limb salvage at 12 months appeared significantly greater in the SCS group (risk difference (RD) − 0·13 (95 per cent confidence interval (c.i.) − 0·04 to − 0·22)). Significant pain relief occurred in both treatment groups, but patients who received SCS required significantly less analgesia and reached Fontaine stage 2 more often than those who did not have SCS (RD 0·33 (95 per cent c.i. 0·19 to 0·47)). Complications of SCS were problems of implantation (8·2 per cent), changes in stimulation requiring reintervention (14·8 per cent) and infection (2·9 per cent). Conclusion The addition of SCS to standard conservative treatment improves limb salvage, ischaemic pain and the general clinical situation in patients with inoperable chronic critical leg ischaemia. These benefits should be weighed against the cost and the (minor) complications associated with the technique. Introduction Treatment of chronic critical leg ischaemia is often a challenge; co-morbidity and mortality rates are high because of the systemic presence of atherosclerosis. The natural history is difficult to describe owing to differences in definition used by various authors and the proportion of patients revascularized in different series. It is estimated that 10–30 per cent of patients with chronic critical leg ischaemia will die within 6 months of its onset and another 25–35 per cent will undergo a major amputation1. Revascularization is the therapy of choice to relieve ischaemic rest pain, to heal ischaemic ulcers and to avoid major loss of limb1. Nevertheless, patients remain for whom vascular surgery has no realistic chance of success, despite technical progress. Their pain is often disabling, adversely affecting quality of life and limiting activity severely. The only option for these patients is generally conservative treatment, with analgesics, vasodilators and/or anticoagulants before amputation ultimately becomes necessary. Alternative or additional therapies have been sought to improve limb salvage and quality of life. These include prostaglandins and spinal cord stimulation (SCS). The latter, in particular, has been proposed as an aid in the management of chronic, intractable pain of the trunk or limbs. It requires insertion of an electrode into the epidural space connected to a subcutaneously sited impulse generator, which invokes paraesthesia in the area of pain. Several preclinical and clinical studies of SCS have been performed to investigate its potential beneficial effects, including improved limb salvage, pain relief and ulcer healing. Cook et al.2 were the first to use SCS in patients with peripheral vascular disease; they reported a striking relief of pain and increased healing of ulcers2. In other publications, SCS appeared to provide good to excellent pain control (in 60–82 per cent of patients)3–11, a reduction in oral analgesic requirement6,9,12, an improvement in claudication distance13, and an improvement in the activities of daily living3,8,9,12,14. These apparent benefits of SCS on the ischaemic leg could be attributed to an improvement in the microcirculatory status of the limb. The nutrition of the skin is determined by the blood flow in the peripheral microcirculation. Several authors have reported an increase in direct and indirect variables reflecting skin microcirculation, such as capillary flow and density of capillaries perfused4, and skin temperature of the foot15,16. Local transcutaneous oxygen tension (Ptco2) has been suggested as a predictor of success10,17–21. However, few studies of SCS were randomized or controlled and so the overall effect on limb salvage and other beneficial endpoints has not yet been clearly established18,22–25. In this systematic review the authors attempt to identify and summarize the evidence for an effect of SCS on limb salvage, pain, wound healing and quality of life in the treatment of patients with inoperable chronic critical leg ischaemia; complications and costs are also analysed. A more detailed account may be found in the Cochrane Database of Systematic Reviews26. Methods All randomized clinical trials (RCTs) and controlled clinical trials (CCTs) evaluating the effectiveness of SCS in patients with inoperable disease were eligible. To conform to the TransAtlantic Inter-Society Consensus definition of chronic critical leg ischaemia1, these studies had to present an objective measure, such as a systolic ankle blood pressure less than 50 mmHg, toe blood pressure below 30 mmHg and/or Ptco2 less than 30 mmHg, to ensure that the clinical manifestations of leg ischaemia were indeed caused by peripheral arterial disease. Studies containing patients suffering from severe peripheral arterial disease defined by peripheral pressures, but without symptoms of chronic critical leg ischaemia (‘subcritical ischaemia’), were excluded. Inoperability was defined as a situation in which the doctor responsible for treating the patient recognized no surgical option to improve the critically ischaemic leg at the time of trial inclusion. This may occur when no crural artery is recognized on the angiogram as a potential site for distal bypass, no suitable vein is available as a conduit, or when the patient's general condition precludes an operation. Patients suffering from critical leg ischaemia solely due to non-atherosclerotic vascular diseases, such as Raynaud's disease or Buerger's disease, were excluded. Milder forms of leg ischaemia, in particular intermittent claudication, were not considered suitable for SCS treatment because this condition does not generally require vascular reconstruction. Relevant reports were sourced from the Specialised Trials Register of the Cochrane Peripheral Vascular Diseases Group, which is compiled by searching bibliographic databases such as Medline and Embase, and the Cochrane Central Register of Controlled Trials. The search was not limited by language or publication status. Authors of included trials and the manufacturer of nearly all SCS devices (Medtronic, Minneapolis, Minnesota, USA) were contacted for additional data or unpublished studies. Finally, the bibliographies of the trials identified through the search process were themselves searched. Titles and abstracts of references identified by the search were screened independently by two reviewers for their potential relevance and design. Full versions of articles were obtained and checked independently to identify those that fitted the inclusion criteria. Subsequently, the methodological quality of each trial was assessed systematically and independently, according to the Dutch Cochrane Centre list of factors relating to internal and external validity27. Details of the studies found were extracted and summarized independently by two reviewers using a standard data extraction sheet27. If data were missing from reports of trials, attempts were made to contact the authors to obtain missing information. Trials published in duplicate were included only once. Quantitative data were entered into the Cochrane RevMan 4.1 software and analysed using MetaView® (The Cochrane Collaboration, Oxford, UK). For each trial and outcome, summary estimates of treatment effect (with 95 per cent confidence intervals (c.i.)) were calculated for each comparison. For dichotomous (yes/no) outcomes the relative risk (RR) and absolute risk reduction (risk difference (RD)) were calculated, and for continuous outcomes the weighted mean difference28. Pooling of the trial results was performed using a fixed effects model, or a random effects model in situations of heterogeneity of the studies. No pooling could be performed when an endpoint was addressed by only one study, or when the standard deviation was not given. Results Study descriptions Eighteen reports were found on the basis of the inclusion criteria, nine of which were excluded. Four of these were excluded because they were not RCTs or CCTs13,29–31. One reference contained only a description of study design32, and one included patients in whom reconstruction was possible33. Three reports were duplicate publications34–36. The remaining nine reports, all published since 1994, described six trials. Five were national studies: one Belgian24, one Swedish23, one German18 and two Dutch22,37. One was a recent European multinational CCT25. The study size varied from 37 to 120 patients and totalled 444 participating patients. Four of the nine papers focused on the Dutch Epidural Spinal Electrical Stimulation (ESES) Study20,22,38,39. All studies included inoperable patients with chronic critical leg ischaemia (either ischaemic rest pain or ulcers smaller than 3 cm in diameter), on the basis of clinical symptoms, peripheral blood pressure variables and angiographic findings. The proportion of patients with ischaemic rest pain without ulceration ranged from 24 to 49 per cent. In the German study18, only patients with ischaemic ulcers were included, whereas in the Belgian study24 11 patients with Buerger's disease were also enrolled. These 11 patients were excluded from the limb salvage meta-analysis. In all studies, patients received control treatment with or without SCS. In the German study18 and the European multinational study25 a period of test stimulation was applied before final implantation of the pulse generator. Control treatment consisted of optimum conservative treatment (local wound care, analgesics, anticoagulants and antibiotics if deemed necessary), which was similar among the studies. In the German study18, additional prostaglandin therapy was given to both groups. In two trials Ptco2 measurements were used for patient classification20,25. All authors used limb salvage (major amputation rate after 12 months) as the primary endpoint. A major amputation was defined in all papers as an amputation at foot level or higher. Pain relief and clinical Fontaine stage were scored by most authors, and complications of SCS and quality of life were detailed by some. Methodological quality All studies were RCTs, except for the European multinational study25, which was a CCT. The methodological study characteristics are shown in Table 1; overall the quality was good. However, blinding of the treating doctors and of the patients was not possible owing to the nature of the technique. The reviewers of effect were, likewise, not blinded. In most studies many patients died during follow-up, hardly surprising in an aged group suffering from generalized atherosclerosis. The mortality rate did not differ between patients treated with or without SCS. Patients who died were accounted for in all studies and censored at death in the analyses. Table 1 Characteristics of included studies Reference . Study description . Valid no.* . Follow-up (months) . Study endpoints . 1 . 2 . 3 . 4 . 5 . 6 . 7 . 24 3 university hospitals in Belgium  27 Up to 12 Limb salvage, pain relief, Fontaine stage, complications Yes ? Yes Yes No Yes Yes 23 2 university hospitals in Sweden  51 Up to 60 Limb salvage, pain relief, ABPI, toe pressure, complications Yes ? Yes Yes No Yes ? 18 University hospital in Germany  86 Up to 12 Limb salvage, pain relief, ABPI, Fontaine stage, complications, Ptco2 Yes ? Yes Yes No Yes Yes 22 17 Dutch centres* 120 Up to 24 Limb salvage, pain relief, Fontaine stage, QoL, ABPI, complications Yes Yes Yes Yes No Yes Yes 20 17 Dutch centres* 111 Up to 24 Limb salvage, Ptco2 Yes Yes Yes Yes No Yes Yes 37 Dutch centres†  37 18 Limb salvage, pain relief Yes Yes Yes Yes No Yes Yes 38 17 Dutch centres* 120 Up to 24 Limb salvage, pain relief, QoL Yes Yes Yes Yes No Yes Yes 39 17 Dutch centres* 120 Up to 24 Limb salvage, pain relief, complications Yes Yes Yes Yes No Yes Yes 25 17 European centres 112 Up to 18 Limb salvage, pain relief, QoL, Fontaine stage, complications, Ptco2 No n.a. Yes n.a. No Yes Yes Reference . Study description . Valid no.* . Follow-up (months) . Study endpoints . 1 . 2 . 3 . 4 . 5 . 6 . 7 . 24 3 university hospitals in Belgium  27 Up to 12 Limb salvage, pain relief, Fontaine stage, complications Yes ? Yes Yes No Yes Yes 23 2 university hospitals in Sweden  51 Up to 60 Limb salvage, pain relief, ABPI, toe pressure, complications Yes ? Yes Yes No Yes ? 18 University hospital in Germany  86 Up to 12 Limb salvage, pain relief, ABPI, Fontaine stage, complications, Ptco2 Yes ? Yes Yes No Yes Yes 22 17 Dutch centres* 120 Up to 24 Limb salvage, pain relief, Fontaine stage, QoL, ABPI, complications Yes Yes Yes Yes No Yes Yes 20 17 Dutch centres* 111 Up to 24 Limb salvage, Ptco2 Yes Yes Yes Yes No Yes Yes 37 Dutch centres†  37 18 Limb salvage, pain relief Yes Yes Yes Yes No Yes Yes 38 17 Dutch centres* 120 Up to 24 Limb salvage, pain relief, QoL Yes Yes Yes Yes No Yes Yes 39 17 Dutch centres* 120 Up to 24 Limb salvage, pain relief, complications Yes Yes Yes Yes No Yes Yes 25 17 European centres 112 Up to 18 Limb salvage, pain relief, QoL, Fontaine stage, complications, Ptco2 No n.a. Yes n.a. No Yes Yes * Four Dutch studies reported on the same patient group (Epidural Spinal Electrical Stimulation (ESES) Study22), which was included only once in the meta-analysis. † Patient set different from ESES Study patients. ABPI, ankle : brachial pressure index; Ptco2, transcutaneous oxygen pressure; QoL, quality of life analysis; 1, randomization; 2, allocation concealment; 3, sufficient follow-up; 4, intention to treat; 5, blinding; 6, group comparability at baseline; 7, similar treatment apart from intervention;?, insufficent information; n.a., not applicable. Open in new tab Table 1 Characteristics of included studies Reference . Study description . Valid no.* . Follow-up (months) . Study endpoints . 1 . 2 . 3 . 4 . 5 . 6 . 7 . 24 3 university hospitals in Belgium  27 Up to 12 Limb salvage, pain relief, Fontaine stage, complications Yes ? Yes Yes No Yes Yes 23 2 university hospitals in Sweden  51 Up to 60 Limb salvage, pain relief, ABPI, toe pressure, complications Yes ? Yes Yes No Yes ? 18 University hospital in Germany  86 Up to 12 Limb salvage, pain relief, ABPI, Fontaine stage, complications, Ptco2 Yes ? Yes Yes No Yes Yes 22 17 Dutch centres* 120 Up to 24 Limb salvage, pain relief, Fontaine stage, QoL, ABPI, complications Yes Yes Yes Yes No Yes Yes 20 17 Dutch centres* 111 Up to 24 Limb salvage, Ptco2 Yes Yes Yes Yes No Yes Yes 37 Dutch centres†  37 18 Limb salvage, pain relief Yes Yes Yes Yes No Yes Yes 38 17 Dutch centres* 120 Up to 24 Limb salvage, pain relief, QoL Yes Yes Yes Yes No Yes Yes 39 17 Dutch centres* 120 Up to 24 Limb salvage, pain relief, complications Yes Yes Yes Yes No Yes Yes 25 17 European centres 112 Up to 18 Limb salvage, pain relief, QoL, Fontaine stage, complications, Ptco2 No n.a. Yes n.a. No Yes Yes Reference . Study description . Valid no.* . Follow-up (months) . Study endpoints . 1 . 2 . 3 . 4 . 5 . 6 . 7 . 24 3 university hospitals in Belgium  27 Up to 12 Limb salvage, pain relief, Fontaine stage, complications Yes ? Yes Yes No Yes Yes 23 2 university hospitals in Sweden  51 Up to 60 Limb salvage, pain relief, ABPI, toe pressure, complications Yes ? Yes Yes No Yes ? 18 University hospital in Germany  86 Up to 12 Limb salvage, pain relief, ABPI, Fontaine stage, complications, Ptco2 Yes ? Yes Yes No Yes Yes 22 17 Dutch centres* 120 Up to 24 Limb salvage, pain relief, Fontaine stage, QoL, ABPI, complications Yes Yes Yes Yes No Yes Yes 20 17 Dutch centres* 111 Up to 24 Limb salvage, Ptco2 Yes Yes Yes Yes No Yes Yes 37 Dutch centres†  37 18 Limb salvage, pain relief Yes Yes Yes Yes No Yes Yes 38 17 Dutch centres* 120 Up to 24 Limb salvage, pain relief, QoL Yes Yes Yes Yes No Yes Yes 39 17 Dutch centres* 120 Up to 24 Limb salvage, pain relief, complications Yes Yes Yes Yes No Yes Yes 25 17 European centres 112 Up to 18 Limb salvage, pain relief, QoL, Fontaine stage, complications, Ptco2 No n.a. Yes n.a. No Yes Yes * Four Dutch studies reported on the same patient group (Epidural Spinal Electrical Stimulation (ESES) Study22), which was included only once in the meta-analysis. † Patient set different from ESES Study patients. ABPI, ankle : brachial pressure index; Ptco2, transcutaneous oxygen pressure; QoL, quality of life analysis; 1, randomization; 2, allocation concealment; 3, sufficient follow-up; 4, intention to treat; 5, blinding; 6, group comparability at baseline; 7, similar treatment apart from intervention;?, insufficent information; n.a., not applicable. Open in new tab Outcome variables Limb salvage Five studies did not show a significant difference in amputation frequencies after 12, 18 or 24 months of follow-up18,22–25, although all studies showed a trend towards a better amputation-free salvage in the SCS group37. This trend was stronger in a subgroup of patients selected by initial Ptco2 than overall (P = 0·17 versus P = 0·47 respectively)20. In one study, the difference in cumulative limb salvage rate was significantly better for patients treated with SCS (P = 0·003), particularly so in a subgroup selected by initial Ptco2 and response to trial stimulation (P = 0·002)25. The a priori risk of amputation, that is the amputation prevalence in the whole patient group irrespective of the treatment given, was about 50 per cent (range 46–64 per cent) in all but one study (in which it was 17 per cent, possibly because both groups also received prostaglandin treatment18). Pooling of the results yielded a significant effect in favour of SCS after 12 months: RR 0·71 (95 per cent c.i. 0·56 to 0·90), RD − 0·13 (95 per cent c.i. − 0·04 to − 0·22) (Fig. 1). This effect did not change after exclusion of the single non-randomized study25 (RR 0·74 (95 per cent c.i. 0·56 to 0·96), RD 0·12 (95 per cent c.i. 0·02 to 0·22)) or the German study18, which included only patients in Fontaine stage 4 (RR 0·70 (95 per cent c.i. 0·55 to 0·89), RD 0·15 (95 per cent c.i. 0·05 to 0·26)). This result means that eight patients need to be treated to prevent one more major amputation (number needed to treat (NNT) 8 (95 per cent c.i. 5 to 25)). Fig. 1 Open in new tabDownload slide Meta-analysis of 12-month amputation rates. Values in parentheses and whiskers represent 95 per cent confidence intervals. SCS, spinal cord stimulation. Test for heterogeneity: χ2 = 3·03, 5 d.f., P = 0·70, I2 = 0 per cent. Test for overall effect: Z = 2·88, P = 0·004 Pain relief As judged by a visual analogue scale, pain relief was significantly better in the SCS group after 3 months (P < 0·001)37 and 12 months (P < 0·01)23. In one study38, a highly significant reduction in pain score (from a mean of 50 to 25) was found during follow-up, but no difference between the two treatment groups. The pain rating index, as part of the McGill pain questionnaire, also showed a significant decrease during follow-up in both groups38. During follow-up, patients receiving SCS used significantly less non-narcotic and narcotic analgesia than those treated conservatively22,38, as measured by the medication quantification scale. In patients who underwent a major amputation during the follow-up period the visual analogue scale score declined significantly (P < 0·001) in both treatment groups. This held also for the pain rating index (P = 0·001). Therefore, pain relief in amputated patients was substantially better than that in non-amputated patients, irrespective of the treatment38. Pooling could not be performed owing to missing standard deviations. Clinical improvement In two studies the number of patients whose clinical stage improved from chronic critical leg ischaemia to claudication was significantly higher in the SCS than in the conservative group (P = 0·001)18,24. For the pooled studies the RR was 4·9 (95 per cent c.i. 2·0 to 11·9) and the RD 0·33 (95 per cent c.i. 0·19 to 0·47) (Fig. 2). This means three patients had to be treated with SCS for one patient to reach Fontaine stage 2 (NNT 3 (95 per cent c.i. 2 to 5)). Fig. 2 Open in new tabDownload slide Meta-analysis of clinical improvement from critical leg ischaemia to claudication. Values in parentheses and whiskers represent 95 per cent confidence intervals. SCS, spinal cord stimulation. Test for heterogeneity: χ2 = 0·37, 1 d.f., P = 0·54, I2 = 0 per cent. Test for overall effect: Z = 4·66, P < 0·001 Two studies reported on the healing of ischaemic ulcers18,22. One showed SCS to have a significantly better effect on wound healing than conservative treatment (P = 0·013)18; the other showed no significant difference22. Pooling demonstrated no significant difference between the two treatment modalities. No significant differences in treatment effect were found between diabetics and non-diabetics18,22. Ankle : brachial pressure index In one study the change in ankle : brachial pressure index (ABPI) after 12 months was significantly different (P < 0·02) between patients having SCS (+0·03; 10 per cent higher than at baseline) and those treated conservatively group (−0·06; 17 per cent lower than at baseline)18. However, in another study there was no change in ABPI in either group during treatment23. Pooling could not be performed owing to missing standard deviations. Quality of life An SF-12 questionnaire was used during follow-up in one study, but only for patients who had SCS25. This showed no worsening of the overall quality of life. In another study, the Nottingham Health Profile (NHP) and the Euroqol were applied in both treatment groups38. The overall score of the NHP decreased (improved) during follow-up in both treatment groups. The mobility score of the NHP was significantly better in the patients treated with SCS (P < 0·01). In patients who had an amputation mobility was reduced and was not influenced by rehabilitation programmes. The Euroqol also showed an improvement after 12 months in the SCS and conservative groups (from 54 to 11 and from 51 to 10 respectively). After amputation these scores worsened to 66 and 61 respectively, but recovered over a period of several months to values of non-amputated patients. Transcutaneous oxygen tension In one study, foot skin Ptco2 was similar in both groups at baseline (10 versus 12 mmHg in SCS and conservative treatment groups respectively) and was significantly higher in the SCS group after 12 months of treatment (21 versus 11 mmHg; P < 0·001)18. In another study, Ptco2 was similar at baseline (10 mmHg in both groups) and increased significantly (P < 0·05) during follow-up, but was not significantly different between groups20. This was found after carrying forward the results before amputation. Only the mean Ptco2 results after 12 months could be pooled. Using a random effects model, no significant difference could be detected. Complications No differences in mortality were observed. Usually only the complications of SCS treatment were described. In one trial the noted side-effects of medical treatment in the conservative group of 60 patients were upper gastrointestinal bleeding (three), nausea (seven) and dizziness (two); among the 60 patients in the SCS group they were duodenal perforation (one), nausea (two) and pruritus (one)22. Initial implantation difficulty was due to technical or anatomical problems causing failure of positioning the electrode in the epidural space and occurred in two trials. In the first, two of a total of 75 patients could not be implanted25; in the second this occurred in nine of 60 patients39. After pooling, the risk of implantation problems was 8·2 (95 per cent c.i. 4·1 to 14·1) per cent, implying that in about every 12th patient an implantation difficulty could be expected. All trials reported the number of changes in stimulation requiring a surgical reintervention. Such changes included dislocation of the electrode and fracture of the lead. Multicentre trials showed the highest incidence of complication22,25. Pooling resulted in a risk of 14·8 (95 per cent c.i. 10·0 to 19·6) per cent. Infection of the lead or subcutaneous pulse generator pocket occurred less frequently. The pooled risk from the six studies was 2·9 (95 per cent c.i. 1·1 to 6·1) per cent. Depletion of the battery within 18 months of follow-up also occurred—in five patients in one study25 and in three in another39. The overall number of complications of SCS treatment, comprising infection of lead or impulse generator pocket, dislocation or breakage of the lead, and early depletion of the battery, was pooled over the six trials. The mean incidence was 20·9 (range 4·0–43·9) per cent. The highest rates, 26·7 and 43·9 per cent, occurred in multicentre trials22,25. Overall complication risk in a random effects model was 0·18 (95 per cent c.i. 0·03 to 0·32), indicating a number needed to harm of 6 (95 per cent c.i. 3 to 33). Costs A cost comparison was made only in the paper from the ESES Study Group22. The mean overall costs of hospitalization, rehabilitation, operative procedures, stimulator, outpatient care, professional home care, medication and non-medical costs at 2 years were €36 500 in the SCS group and €28 600 in the conservative group (P < 0·009). After adjustment for mortality these figures were €31 340 and €23 780 respectively (P = 0·002). Discussion There is evidence that SCS is better than conservative treatment alone in achieving a reduction in amputation risk and pain relief, and an improvement in general clinical situation in patients with inoperable, chronic critical leg ischaemia. The effect of SCS appears to be stronger after further patient selection on the basis of a beneficial Ptco2 and test stimulation period. This beneficial effect should be weighed against the harm SCS may induce (basically implantation failure) and its relatively minor associated complications. In addition, the impact of SCS treatment on healthcare budgets needs to be considered. If pain relief is the primary goal, less expensive options are readily available, and a major amputation may be the treatment of choice in patients with an already limited mobility. The higher complication rate typical of multicentre studies enrolling few patients per centre suggests that this treatment should be carried out in specialist units that have the appropriate facilities and expertise. Compared with the large total number of publications on SCS for inoperable leg ischaemia, only a few randomized studies exist. One reason may be the limited number of patients with leg ischaemia who are regarded as inoperable and so eligible candidates for such a trial. The chance of publication bias is regarded as small; the manufacturer of nearly all SCS devices is tracking all studies that are or have been performed on SCS in this type of patient. The trials included here all focused on limb salvage, clinical improvement and complications; few addressed quality of life and cost. It might be thought that limb salvage results could be biased if amputation was postponed in SCS-treated patients, but progressive necrosis with imminent sepsis and intractable pain despite maximum analgesic therapy, which was allowed in both treatment groups, were the absolute indications for amputation. The results of some secondary endpoints (such as ABPI and Ptco2) may be considered problematic as they are influenced by the loss of patients undergoing an amputation during follow-up, which leaves only the ‘better’ patients; positive bias is the result. Pooled data, but not the individual RCTs, revealed a significant beneficial effect in terms of limb salvage, at the cost of a significantly higher number of correctable complications and apparently higher costs. The finding that eight patients need to be treated to save one more leg, together with the higher cost of SCS treatment (about €8000 for 2 years), suggests that about €64 000 extra needs to be spent to achieve this end. This should be weighed against any improvement in quality-adjusted life-years and the eventual cost of a major amputation, itself accompanied by ongoing high costs and a high mortality rate. In additional, there is some evidence of ulcer healing and pain relief with SCS. The finding that Ptco2, but not ABPI, seems to increase during follow-up suggests that SCS treatment acts mainly on the local microcirculation. Pain relief and ulcer healing may also improve walking ability, which may further enhance local circulation. The general quality of life seemed to remain unchanged, although a trend towards an improvement was noted in both treatment groups. Quality of life may be influenced by other major factors, or the questionnaires used may be too insensitive to measure specific changes due to leg ischaemia or its treatment. To date, no specific validated questionnaires exist with which to assess quality of life in chronic limb ischaemia. Major amputation can still be considered as a reasonable alternative treatment as it provides good pain relief, albeit at the cost of a reduction in mobility. Criteria in future studies should include patients who are most likely to benefit from this treatment. Ptco2 monitoring to assess the local microcirculation and a period of test stimulation both appear useful for this purpose. Usually, variables such as Ptco2 are calculated during follow-up without carrying forward the data obtained from those who previously underwent amputation. 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TI - Systematic review and meta-analysis of controlled trials assessing spinal cord stimulation for inoperable critical leg ischaemia
JO - British Journal of Surgery
DO - 10.1002/bjs.4629
DA - 2004-07-27
UR - https://www.deepdyve.com/lp/oxford-university-press/systematic-review-and-meta-analysis-of-controlled-trials-assessing-cauTIgY0V0
SP - 948
EP - 955
VL - 91
IS - 8
DP - DeepDyve
ER -