Main Article Content

Héctor Álvarez Duarte
José I Fernández Montequín
Martha M Fors López
José Hernández Carretero
Miriam Mahia Vilas
Milagros García Mesa


Diabetic foot, sepsis, amputation, Procaine, Polyvinylpyrrolidone De Marco Formula



De Marco Formula (DMF) is a novel formulation of procaine and PVP.



To assess the efficacy and safety of DMF as an adjunctive therapy for infected ischemic diabetic foot in a prospective randomized controlled clinical trial.



Adult patients, 39 male/ 79 female, were randomly assigned (59 patients/treatment group) to the conventional therapy alone (A) or plus DMF (0, 15 ml/kg .day i.m.) during ten days and them twice a week until healing of the lesions or completion of 52 days (B). The response to the treatment was considered favorable when an amputation was not needed even though a decrease of the wound area or complete healing was not shown. It was considered unfavorable when a major amputation was necessary because of worsening of the lesion (wound spreading to any magnitude greater than the initial one) or the appearance of new wounds in the same leg.



Both groups were comparable with regard to age, sex, level of arterial occlusion, type of lesion, anatomic localization of lesions and previous surgical procedures. The cumulative percentage of unfavorable results was significantly lower after treatment B with respect to treatment A (25.4% vs. 45.8%; p= 0.02), for a reduction of 44.5%. Four slight adverse reactions were associated with DMF: vertigo and nausea at the 7th treatment administration (one patient), and headache and tachycardia at the 12th dose (another patient). Blood hemoglobin and leukocyte counts and serum alanine transaminase were not affected.



The treatment with DMF for 52 days as an adjuvant for the conventional therapy was associated with a lower need for major amputations. It was also well tolerated and safe.

Abstract 104 | PDF Downloads 42


1. Viswanathan V. The diabetic foot: perspectives from Chennai, South India. Int J Low Extrem Wounds 2007;6:34-6.
2. Rathur HM, Boulton AJ. The diabetic foot. Clin Dermatol 2007;25:109-20.
3. Rathur HM, Boulton AJ. The neuropathic diabetic foot. Nat Clin Pract Endocrinol Metab 2007;3:14-25.
4. Delmas L. Best practice in the assessment and management of diabetic foot. Ulcers Rehabil Nurs 2006;31:228-34.
5. Schramm JC, Dinh T, Veves A. Microvascular changes in the diabetic foot. Int J Low Extrem Wounds 2006;5:149-59.
6. Wieman TJ. Principles of management: the diabetic foot. Am J Surg 2005;190:295-9.
7. Younes NA, Albsoul AM, Awad H. Diabetic heel ulcers: a major risk factor for lower extremity amputation. Ostomy Wound Manage 2004;50:50-60.
8. Brem H, Jacobs T, Vileikyte L, et al. Woundhealing protocols for diabetic foot and pressure ulcers. Surg Technol Int 2003;11:85- 92.
9. Brem H, Sheehan P, Rosenberg HJ, Schneider JS, Boulton AJ. Evidence-based protocol for diabetic foot ulcers. Plast Reconstr Surg 2006;117(7Suppl):193S-209S; discussion 210S-11S.
10. Van Damme H, Limet R. The diabetic foot. Rev Med Liege 2005;60:516-25.
11. McCook J. Pie Diabético: Epidemiología. Rev Cubana Hig Epidemiol 1979;17(58):163- 73.
12. Boutoille D, Leautez S, Maulaz D, Krempf M, Raffi F. Ulcers of the diabetic foot: Epidemiology and Physiopathology. Presse Med. 2000;29:389-92.
13. Vejerano García P, Rivero Fernández F, Gónzalez Gónzalez F. Morbilidad y mortalidad por pie diabético en nuestro servicio. Rev Cubana Endocrinol 1990;1:142- 7.
14. Watkins PJ. ABC of diabetes: The diabetic foot BMJ 2003;326:977-9.
15. Edmonds ME. ABC of wound healing: Diabetic foot ulcers. BMJ 2006;332:407-10.
16. Lima Santana B. Reamputaciones de miembros inferiores en pacientes diabéticos. Rev Cub Cirugia 1982;21:194–202.
17. Lobmann R, Gregory S, Lobmann R. Proteases and the Diabetic Foot Syndrome: Mechanisms and Therapeutic Implications. Diabetes Care 2005;28:461-71.
18. Ebskov LB. Relative mortality in lower extremity amputees with diabetes mellitus. Prosthet Orthot Int 1996;20:147-52.
19. Ebskov B, Ebskov L. Major lower extremity amputation in diabetic patients: development during 1982 to 1993. Diabetologia 1996;39:1607-10.
20. Baulton AJ. Why bother educating the multi disciplinary team and the patients; the example of prevention of lower extremity amputation in diabetes. Patient Educ Couns 1995;26:183-8.
21. Heng MC, Harker J, Csathy G, et al. Angiogenesis in necrotic ulcers treated with hyperbaric oxygen. Ostomy Wound Manage 2000;46:18-28.
22. de Lalla F, Pellizzer G, Strazzabosco M, et al. Randomized prospective controlled trial of recombinant granulocyte colony-stimulating factor as adjunctive therapy for limbthreatening diabetic foot infection. Antimicrob Agents Chemother 2001:45;1094-8.
23. Lipsky BA, Berendt AR, Deery HG, et al. Infectious Diseases Society of America. Diagnosis and treatment of diabetic foot infections. Plast Reconstr Surg 2006;117 (Suppl):212S-38S.
24. Zhang JG, Esposito M, Cafaggi S, Lindup WE. Comparison of the toxicities of cisplatin and a new cisplatin-procaine complex to rat renal cortical slices. Hum Exp Toxicol 1996;15:59-63.
25. Zhang JG, Lindup WE. Cisplatin-induced changes in adenine nucleotides in rat kidney slices: amelioration by tiopronin and procaine. J Pharm Pharmacol 1997;49: 1136-40.
26. Viale M, Vannozzi MO, Pastrone I, et al. Reduction of cisplatin nephrotoxicity by procainamide: does the formation of a cisplatin-procainamide complex play a role? J Pharmacol Exp Ther 2000;293:829-36.
27. Zicca A, Cafaggi S, Mariggiò, et al. Reduction of cisplatin hepatotoxicity by procainamide hydrochloride in rats. Eur J Pharmacol 2002;10(442): 265-72.
28. Fenoglio C, Boicelli CA, Ottone M, Addario C, Chiari P, Viale M. Protective effect of procaine hydrochloride on cisplatin-induced alterations in rat kidney. Anticancer Drugs 2002;13:1043-54.
29. de Klaver MJ, Weingart GS, Obrig TG, Rich GF. Local anesthetic-induced protection against lipopolysaccharide-induced injury in endothelial cells: the role of mitochondrial adenosine triphosphate-sensitive potassium channels. Anesth Analg 2006;102:1108-13.
30. Takagi S, Kitagawa S, Oshimi K, Takaku F, Miura Y. Effect of local anesthetics on human natural killer cell activity. Clin Exp Immunol 1983;53:477-81.
31. Bekemeier H, Hirschelmann R. Antiphlogistic effectiveness of combinations of inhibitors of phospholipase A2, cyclooxygenase and lipoxygenases of the arachidonic acid cascade. Pharmazie 1986;41:260-2.
32. Sasagawa S. Inhibitory effects of local anesthetics on migration, extracellular release of lysosomal enzyme, and superoxide anion production in human polymorphonuclear leukocytes. Immunopharmacol Immunotoxicol 1991;13:607-22.
33. Hattori M, Dohi S, Nozaki M, Niwa M, Shimonaka H. The inhibitory effects of local anesthetics on superoxide generation of neutrophils correlate with their partition coefficients. Anesth Analg 1997;84:405-12.
34. Dolganiuc A, Radu D, Olinescu A, Vr?biescu A. Procain and diethylaminoethanol influence on the release of free oxygen radicals by polymorphonuclear leukocytes, in rabbits and humans. Roum Arch Microbiol Immunol 1998;57:23-32.
35. Bordea M, Ardeleanu C, Dolganiuc A, Olinescu A, Vr?biescu A. Morpho-functional aspects of the influence of procaine and diethylaminoethanol treatment on the immune system of rabbits. Rom J Physiol 1998;35:111-26.
36. Pigeolet E, Raes M, Houbion A, Remacle J. Effect of procaine on cultivated human WI-38 fibroblasts. Exp Gerontol 1988;23:87-96.
37. Banerjee D, Redman CM. Effect of local anesthetics on plasma protein secretion by rat hepatocytes. Biochim Biophys Acta 1977;500:49-60.
38. Yamaguchi T, Beppu M, Terao T, Osawa T. Effect of local anesthetics on the inhibition of protein synthesis by ricin. J Pharmacobiodyn 1982;5:686-92.
39. Kaemmerer K, Kietzmann M. Intermediary effectiveness of procaine and procaine metabolites following oral administration. ZFA 1989;44:189-99.
40. Pelz K, Wiedmann-Al-Ahmad M, Bogdan C, Otten JE. Analysis of the antimicrobial activity of local anaesthetics used for dental analgesia. J Med Microbiol 2008;57: 88-94.
41. Huang Y, Lau CW, Chan FL, Yao XQ. Contribution of nitric oxide and K+ channel activation to vasorelaxation of isolated rat aorta induced by procaine. Eur J Pharmacol 1999;367:231-7.
42. Garden JM, Altman GD. Statistics with Confidence. BMJ, London:WC1H 9JR, 1994.
43. Karch FE, Lasagna L. Toward the operational identification of adverse drug reactions. Clin Pharmacol Ther 1977;21:247-54.