From the Department of Neurosurgery, University Hospital, Maastricht, The Netherlands, the *Department of Vascular Surgery, Univer- sity Hospital Dijzigt, Rotterdam, The Netherlands, and the **Department of Public Health, Erasmus University, Rotterdam, The Nether- lands Spinal Cord Stimulation in Patients with Critical Limb Ischemia: A Preliminary Evaluation of a Multicentre Trial G. H. Spincemaille, H. M. Klomp*, E. W. Steyerberg**, and J. D. F. Habbema** for the ESES study group Keywords: Critical limb ischemia – spinal cord stimulation (SCS) – ischemic pain – limb salvage. Schlüsselwörter: Kritische Beinischämie – Rückenmarkstimula- tion (RMS) – ischämischer Schmerz – Extremitätenerhaltung. Summary: Background : Spinal cord stimulation (SCS) is known to reduce chronic pain. The technique was offered to pa- tients with critical limb ischemia due to atherosclerosis, in which vascular reconstruction was not possible. Methods : 37 patients were randomized for standard treatment with analgesics and vasoactive drugs (n = 18) or electrical stim- ulation of the spinal cord in addition to the standard treatment (n = 19). The primary outcome measures were pain relief and limb salvage. Follow-up covered a period of 4 years. Results : Amputation-free survival at 2 years was 39 % for stan- dard treatment and 61 % for the stimulation plus standard treat- ment (p = 0.08, NS). Most amputations occurred within the first year after randomization. Pain relief was statistically signifi- cant in favor of the stimulation treatment (p < 0.001). None of the patients with good pain relief in the SCS-group was ampu- tated. Limb salvage of this subgroup in the standard treatment was 75 % at one year. Conclusions : A larger multicenter randomized trial comparing SCS and conservative treatment is required to further establish the value of SCS in the treatment of critical limb ischemia. Fol- low-up of 2 years seems adequate to evaluate the effects of SCS. (Acta Chir. Austriaca 2000; 32: 49–51) Rückenmarkstimulation in der Behandlung bei Patien- ten mit kritischer Beinischämie: Vorläufige Evaluie- rung einer Multizenterstudie Zusammenfassung: Grundlagen : Der schmerzlindernde Effekt der epiduralen Rückenmarkstimulation (RMS) ist bei Patienten mit chronischen Schmerzen wiederholt nachgewiesen worden. Wir berichten über unsere Erfahrung mit der RMS bei Patienten mit austherapierter kritischer Extremitätenischämie. Methodik : In einer prospektiven Studie wurden 37 Patienten in 2 Gruppen randomisiert, in eine Gruppe (n = 18), die mit einer „Standardbehandlung“ (Analgetika und vasoaktive Medikation) behandelt wurden, und in eine Gruppe (n = 19), die zusätzlich stimuliert worden ist. Alle Patienten wurden in ein standardisier- tes Nachsorgeprogramm aufgenommen, das die schmerzhem- menden Effekte sowie Amputationsrate dokumentiert. Der Fol- low-up betrug durchschnittlich 4 Jahre. Ergebnisse : Die Extremitätenerhaltung betrug nach 2 Jahren 39 % für die Gruppe mit „Standardtherapie” und 61 % für die Gruppe, welche zusätzlich stimuliert wurde. Dieses Ergebnis war jedoch statistisch nicht signifikant (p = 0,08). Die meisten Amputationen traten innerhalb des 1. Jahres nach Randomisie- rung auf. Der schmerzhemmende Effekt war signifikant besser in der Patientengruppe, die stimuliert worden ist (p < 0,001). Keiner der Patienten mit signifikanter Schmerzlinderung wurde amputiert. Die Extremitätenerhaltung für diese Untergruppe mit „Standardtherapie“ betrug nach einem Jahr 75 %. Schlußfolgerungen : Eine umfangreichere randomisierte Multi- zenterstudie, welche eine konservative Therapie mit der Stimula- tion vergleicht, ist notwendig. Ein Follow-up von 2 Jahren scheint ausreichend zu sein, um die Effekte der Stimulation zu evaluieren. Introduction Peripheral arterial ischemia due to atherosclerosis is a common disease in elderly. Intermittent claudication, a frequent manifes- tation of this disease, progresses to limb-threatening critical ischemia in a small number of patients. The progression is ac- companied by pain at rest, skin ulcers, or both. About 30 to 40 % of patients with peripheral arterial ischemia have diabetes melli- tus (19). Healing of skin ulcers was described as an unexpected effect of spinal cord stimulation (SCS) and transcutaneous stim- ulation in patients treated for various neurological diseases (5, 13). Several authors confirmed an effect of SCS on pain and limb ischemia. (1, 2, 3, 7–12, 21, 28). The hypothesis of a redis- tribution of blood flow was documented by Jacobs (11) using capillary microscopy. Linderoth (17) described inhibition of the sympathetic vasoconstriction in animal experiments. The effects on the macrocirculation are more conflicting and so far any ef- fect is questionable (1, 2, 21). Relief of chronic pain by SCS has been known for years and used in a number of neurological dis- eases (14, 15, 18, 22, 23, 24, 27). Apart from the discussion on the underlying mechanism of SCS, clinicians are interested in a therapy that may increase limb salvage. Important to know is the accuracy of the difference in treatment outcome described in ob- servational studies. Therefore, prospective randomized controll- ed studies are mandatory to prove the effects of SCS on ulcer healing, relief of ischemic pain and limb salvage. Subjects and methods Randomized blocks were used for treatment allocation in each center separately. Eligibility criteria are shown in Table 1. The study was approved by the ethical committee of the hospitals in- volved and patients were enrolled after informed consent was obtained. Follow-up was scheduled at 1, 3, 6, 12, 18 months and yearly thereafter. Standard treatment consisted of analgesics and vasodilating drugs together with optimal care in case of ulcer- ations or gangrene. The experimental treatment consisted of a spinal cord stimulator implantation (Itrel I – Medtronic – Minne- apolis USA) in addition to the standard treatment (26). A spinal cord stimulation system included a lead, an extension cable and a pulse generator. The surgical procedure was performed under local anaesthesia with the patient in prone or lateral position un- der fluoroscopy. The lead was percutaneously placed in the epidural space, using a Touhy needle. In patients with pain in the lower limbs the lead was positioned between the thoracic verte- bral level 11 (Th11) and the first lumbar L1. Proper positioning of the lead was obtained when paresthesias were felt in the pain- ful distal limb region following trial stimulation during the im- plantation. The different parts of the system (lead, extension ca- ble and pulse generator) were implanted subcutaneously and connected with each other. The pulse generator could be con- trolled from outside using an external programmer (Medtronic U.S. Copyright Clearance Center Code Statement: 0001-544-X/2000/3202 – 0049 $15.00/0 Acta Chir. Austriaca ⋅ Vol. 32 ⋅ No 2 ⋅ 2000 49 Corresponding address: G. H. Spincemaille, M.D., Department of Neurosurgery, University Hospital Maastricht, P. Debyelaan 25, NL-6202 AZ-Maastricht, The Netherlands. Fax: ++31/43/387 40 41 E-mail: gspincemaille@sncg.azm.nl Acta Chir. Austriaca ⋅ Vol. 32 ⋅ No 2 ⋅ 2000