, Volume 21, Issue 2, pp 139–148 | Cite as

Cost Effectiveness and Cost Utility of Acetylcysteine versus Dimethyl Sulfoxide for Reflex Sympathetic Dystrophy

  • Hiske E. M. van Dieten
  • Roberto S. G. M. Perez
  • Maurits W. van Tulder
  • Jaap J. de Lange
  • Wouter W. A. Zuurmond
  • Herman J. Ader
  • Hindrik Vondeling
  • Maarten Boers
Original Research Article


Objective: To determine the cost effectiveness and cost utility of acetylcysteine versus dimethyl sulfoxide (DMSO) for patients with reflex sympathetic dystrophy (RSD), from a societal viewpoint.

Design: An economic evaluation was conducted alongside a double-dummy, double-blind, randomised, controlled trial. Patients were followed for 1 year. The primary outcome measure was the Impairment-level Sum Score (ISS). Utilities were determined by the EuroQOL instrument (EQ-5D). Both cost-effectiveness and cost-utility analyses were performed. Differences in mean direct, indirect and total costs were estimated. Corresponding 95% confidence intervals were calculated by bootstrapping techniques.

Results: Both groups (DMSO, n = 64; acetylcysteine, n = 67) showed relevant improvement; no differences in effects were found. Only the total direct costs were significantly lower in the DMSO group for the period of 0–52 weeks. The incremental cost-effectiveness ratios showed that, in general, DMSO generated fewer costs and more effects compared with acetylcysteine. Post-hoc subgroup analyses on cost effectiveness suggested that patients with warm RSD could be best treated with DMSO and patients with cold RSD with acetylcysteine. These results were based on small subsamples.

Conclusion: In general, DMSO is the preferred treatment for patients with RSD.


Spinal Cord Stimulation Acetylcysteine Reflex Sympathetic Dystrophy Pharmacoeconomic Evaluation Travel Expense 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The source of financial support for this economic evaluation was given by the fund of investigative medicine of the Health Insurance Council (OG: 96-014). The authors have provided no information on conflicts of interest directly relevant to the content of this study.


  1. 1.
    Rowlingson JC. The sympathetic dystrophies. Int Anesthesiol Clin 1983; 21: 117–29PubMedCrossRefGoogle Scholar
  2. 2.
    Zuurmond WWA, Langendijk PNJ, Bezemer PB, et al. Treatment of acute reflex sympathetic dystrophy with DMSO 50% in a fatty cream. Acta Anaesthesiol Scand 1996; 40: 364–7PubMedCrossRefGoogle Scholar
  3. 3.
    Veldman PHJM, Goris RJA. Multiple reflex sympathetic dystrophy: which patients are at risk for developing a recurrence of reflex sympathetic dystrophy in the same or another limb. Pain 1996; 64: 463–6PubMedCrossRefGoogle Scholar
  4. 4.
    Jadad AR, Carroll D, Glynn CJ. Intravenous regional sympathetic blockade for pain relief in reflex sympathetic dystrophy: a systematic review and a randomized, double-blind crossover study. J Pain Symptom Manage 1995; 10: 13–20PubMedCrossRefGoogle Scholar
  5. 5.
    Oerlemans HM, Oostendorp RA, de Boo T. Adjuvant physical therapy versus occupational therapy in patients with reflex sympathetic dystrophy/complex regional pain syndrome type I. Arch Phys Med Rehabil 2000 Jan; 81: 49–56PubMedGoogle Scholar
  6. 6.
    Goris RJA. Treatment of reflex sympathetic dystrophy with hydroxyl radical scavengers. Unfallchirurg 1985; 88: 330–2PubMedGoogle Scholar
  7. 7.
    Veldman PHJM, Reynen JAM, Arntz IE. Signs and symptoms of reflex sympathetic dystrophy: prospective study of 829 patients. Lancet 1993; 342: 1012–6PubMedCrossRefGoogle Scholar
  8. 8.
    Oerlemans HM, Goris RJ, Oostendorp RA. Impairment level sumscore in reflex sympathetic dystrophy of one upper extremity. Arch Phys Med Rehabil 1998 Aug; 79 (8): 979–90PubMedCrossRefGoogle Scholar
  9. 9.
    Goossens ME, Rutten-van Molken MP, Vlaeyen JW, et al. The cost diary: a method to measure direct and indirect costs in cost-effectiveness research. J Clin Epidemiol 2000 Jul; 53 (7): 688–95PubMedCrossRefGoogle Scholar
  10. 10.
    Oostenbrink JB, Koopmanschap MA, Rutten FFH. Handleiding voor kostenonderzoek. Apeldoorn: VDA groep, 2000: 1–178Google Scholar
  11. 11.
    Taxe report. The Hague: Royal Dutch Association for the Advancement of Pharmacy, 1999Google Scholar
  12. 12.
    Taxe report: over the counter drugs. The Hague: Royal Dutch Association for the advancement of Pharmacy, 1999Google Scholar
  13. 13.
    Severens JL, Oerlemans HM, Weegels AJPG. Cost-effectiveness analysis of adjuvant physical therapy or occupational therapy for patients with reflex sympathetic dystrophy. Arch Phys Med Rehabil 1999; 80: 1038–43PubMedCrossRefGoogle Scholar
  14. 14.
    Koopmanschap MA, Rutten FF. The consequence of production loss or increased costs of production. Med Care 1996 Dec; 34 (12 Suppl.): DS59–68PubMedGoogle Scholar
  15. 15.
    Briggs AH, Wonderling DE, Mooney CZ. Pulling cost-effectiveness analysis up by its bootstraps: a non-parametric approach to confidence interval estimation. Health Econ 1997 Jul–Aug; 6 (4): 327–40PubMedCrossRefGoogle Scholar
  16. 16.
    Efron B, Tibshirani RJ. An introduction to the bootstrap. New York: Chapman & Hall, 1993Google Scholar
  17. 17.
    Briggs AH, O’Brien BJ. The death of cost-minimization analysis? Health Econ 2001 Mar; 10 (2): 179–84PubMedCrossRefGoogle Scholar
  18. 18.
    Briggs A, Fenn P. Confidence intervals or surfaces?: uncertainty on the cost-effectiveness plane. Health Econ 1998 Dec; 7 (8): 723–40PubMedCrossRefGoogle Scholar
  19. 19.
    Drummond MF, O’Brien B, Stoddart GL. Methods for the economic evaluation of health care programmes. Oxford: University Press, 1999: 68–74Google Scholar
  20. 20.
    Yu ZW, Quinn PJ. Dimethyl sulphoxide: a review of its applications in cell biology. Biosci Rep 1994 Dec; 14 (6): 259–81PubMedCrossRefGoogle Scholar
  21. 21.
    Al MJ, van Hout BA, Michel BC, et al. Sample size calculation in economic evaluations. Health Econ 1998 Jun; 7 (4): 327–35PubMedCrossRefGoogle Scholar
  22. 22.
    Thompson SG, Barber JA. How should cost data in pragmatic randomised trials be analysed? BMJ 2000; 320: 1197–200PubMedCrossRefGoogle Scholar
  23. 23.
    Desagné A, Castilloux A, Angers J, et al. The use of the bootstrap statistical method for the pharmacoeconomic cost analysis of skewed data. Pharmacoeconomics 1998; 13 (5): 487–97CrossRefGoogle Scholar
  24. 24.
    Sacristan JA, Obenchain RL. Reporting cost-effectiveness analyses with confidence. JAMA 1997 Feb 5; 277 (5): 375PubMedCrossRefGoogle Scholar
  25. 25.
    Stinnett AA, Paltiel AD. Estimating CE ratios under second-order uncertainty: the mean ratio versus the ratio of means. Med Decis Making 1997 Oct–Dec; 17 (4): 483–9PubMedCrossRefGoogle Scholar
  26. 26.
    Stinnett AA, Mullahy J. Net health benefits: a new framework for the analysis of uncertainty in cost-effectiveness analysis. Med Decis Making 1998 Apr–Jun; 18 (2 Suppl.): S68–80PubMedCrossRefGoogle Scholar
  27. 27.
    Perez RSGM, Kwakkel G, Zuurmond WA, et al. Medicinal treatment of reflex sympathetic dystrophy (CRPS type 1): a research synthesis of 21 randomised clinical trials. J Pain Symptom Manag 2001b; 21: 511–26CrossRefGoogle Scholar
  28. 28.
    Kemler MA, Furnée CA. Economic evaluation of spinal cord stimulation for chronic reflex sympathetic dystrophy. Thesis: spinal cord stimulation for chronic reflex sympathetic dystrophy. Maastricht, The Netherlands: University of Maastricht, 2000: 93–106Google Scholar

Copyright information

© Adis International Limited 2003

Authors and Affiliations

  • Hiske E. M. van Dieten
    • 1
  • Roberto S. G. M. Perez
    • 2
  • Maurits W. van Tulder
    • 1
  • Jaap J. de Lange
    • 2
  • Wouter W. A. Zuurmond
    • 2
  • Herman J. Ader
    • 1
  • Hindrik Vondeling
    • 3
  • Maarten Boers
    • 1
  1. 1.Department of Clinical Epidemiology & BiostatisticsVrije Universiteit medisch centrumAmsterdamNetherlands
  2. 2.Department of AnesthesiologyVrije Universiteit Medisch CentrumAmsterdamNetherlands
  3. 3.Department of Health EconomicsUniversity of Southern DenmarkOdenseDenmark

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