0

The full content of Annals is available to subscribers

Subscribe/Learn More  >
Articles |

Intravenous Immunoglobulin Treatment of the Complex Regional Pain Syndrome: A Randomized Trial

Andreas Goebel, MD, PhD; Andrew Baranowski, MD; Konrad Maurer, MD; Artemis Ghiai, RGN; Candy McCabe, PhD; and Gareth Ambler, PhD
[+] Article and Author Information

From University of Liverpool, University Hospital Aintree, and the Walton Centre, Liverpool; National Hospital for Neurology and Neurosurgery and Joint University College London Hospitals/University College London Biomedical Research Unit, London; and National Hospital for Rheumatic Diseases, Bath, United Kingdom.


Acknowledgment: The authors thank the participating patients; referring colleagues; Professor Guenter Sprotte for contributions to the study design; Dr. Kahled Ayazi, Dr. Adam Woo, Mrs. Allison MacKenzie, and Dr. Brigitte Brandner for organizational support; Professor Gavin Giovannoni for providing safety advice to the trial; the staff of the Pain Management Centre and clinical laboratory at Queen Square for generous support; and Dr. Geoffrey Schott and Professor Angela Vincent for important suggestions to the manuscript.

Grant Support: By the Association of Anaesthetists of Great Britain and Ireland, the University College London Hospitals Trustees, and CSL-Behring (drugs and contribution to general expenses). This work was undertaken at University College London Hospitals/University College London, which received a proportion of funding from the Department of Health's National Institute for Health Research Biomedical Research Centres funding scheme. The sponsor under International Conference of Harmonisation Good Clinical Practice standards was University College London Hospitals/University College London.

Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M09-1292.

Reproducible Research Statement:Study protocol, statistical code, and data set: Not available.

Requests for Single Reprints: Andreas Goebel, MD, PhD, Pain Research Institute, University of Liverpool, Clinical Sciences Building, University Hospital Aintree, Liverpool L9 7AL, United Kingdom; e-mail, andreasgoebel@rocketmail.com.

Current Author Addresses: Dr. Goebel: Pain Research Institute, University of Liverpool, Clinical Sciences Building, University Hospital Aintree, Liverpool L9 7AL, United Kingdom.

Dr. Baranowski and Mrs. Ghiai: Pain Management Centre, The National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, United Kingdom.

Dr. Maurer: Institute of Anesthesiology, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland.

Dr. McCabe: The National Hospital for Rheumatic Diseases, Upper Borough Walls, Bath BA1 1RL, United Kingdom.

Dr. Ambler: Joint University College London Hospitals/University College London Biomedical Research Unit, Ground Floor, Rosenheim Wing, 25 Grafton Way, London WC1E 6DB, United Kingdom.

Author Contributions: Conception and design: A. Goebel, A. Baranowski, A. Ghiai, G. Ambler.

Analysis and interpretation of the data: A. Goebel, K. Maurer, A. Ghiai, G. Ambler.

Drafting of the article: A. Goebel, A. Baranowski, K. Maurer, A. Ghiai, C. McCabe, G. Ambler.

Critical revision of the article for important intellectual content: A. Goebel, A. Baranowski, K. Maurer, A. Ghiai, G. Ambler.

Final approval of the article: A. Goebel, A. Baranowski, K. Maurer, A. Ghiai, C. McCabe, G. Ambler.

Provision of study materials or patients: A. Goebel, A. Baranowski, C. McCabe.

Statistical expertise: G. Ambler.

Obtaining of funding: A. Goebel.

Administrative, technical, or logistic support: A. Goebel, A. Baranowski, K. Maurer, A. Ghiai, C. McCabe.

Collection and assembly of data: A. Goebel, K. Maurer, A. Ghiai.


Ann Intern Med. 2010;152(3):152-158. doi:10.7326/0003-4819-152-3-201002020-00006
Text Size: A A A

Background: Treatment of long-standing complex regional pain syndrome (CRPS) is empirical and often of limited efficacy. Preliminary data suggest that the immune system is involved in sustaining this condition and that treatment with low-dose intravenous immunoglobulin (IVIG) may substantially reduce pain in some patients.

Objective: To evaluate the efficacy of IVIG in patients with longstanding CRPS under randomized, controlled conditions.

Design: A randomized, double-blind, placebo-controlled crossover trial. (National Research Registry number: N0263177713; International Standard Randomised Controlled Trial Number Registry: 63918259)

Setting: University College London Hospitals Pain Management Centre.

Patients: Persons who had pain intensity greater than 4 on an 11-point (0 to 10) numerical rating scale and had CRPS for 6 to 30 months that was refractory to standard treatment.

Intervention: IVIG, 0.5 g/kg, and normal saline in separate treatments, divided by a washout period of at least 28 days.

Measurements: The primary outcome was pain intensity 6 to 19 days after the initial treatment and the crossover treatment.

Results: 13 eligible participants were randomly assigned between November 2005 and May 2008; 12 completed the trial. The average pain intensity was 1.55 units lower after IVIG treatment than after saline (95% CI, 1.29 to 1.82; P < 0.001). In 3 patients, pain intensity after IVIG was less than after saline by 50% or more. No serious adverse reactions were reported.

Limitation: The trial was small, and recruitment bias and chance variation could have influenced results and their interpretation.

Conclusion: IVIG, 0.5 g/kg, can reduce pain in refractory CRPS. Studies are required to determine the best immunoglobulin dose, the duration of effect, and when repeated treatments are needed.

Primary Funding Source: Association of Anaesthetists of Great Britain and Ireland, University College London Hospitals Charity, and CSL-Behring.

Figures

Grahic Jump Location
Figure 1.
Study flow diagram.

IVIG = intravenous immunoglobulin.

* 11 patients improved, 23 had had complex regional pain syndrome for too long, and 30 did not meet inclusion criteria for other reasons.

† 4 patients had travel problems, 2 declined for other reasons, and 10 declined for unknown reasons.

‡ 1 patient withdrew after becoming pregnant.

Grahic Jump Location
Grahic Jump Location
Figure 2.
Mean pain intensity for each day after the infusion.

Intensities were recorded on an 11-point NRS (0 = no pain and 10 = pain as bad as you can imagine). The horizontal bar marks the 14-day observation period when pain intensities were included in the analyses. Patients received infusions on days 1 and 2. NRS = numerical rating scale.

Grahic Jump Location
Grahic Jump Location
Appendix Figure.
Pain intensity in 13 patients.

Pain intensity for each day after the infusion recorded on an 11-point numerical rating scale (0 = no pain; 10 = pain as bad as you can imagine). The horizontal bars mark the 14-day observation period when pain intensities were included in the analyses. Patients received infusions on days 1 and 2. IVIG = intravenous immunoglobulin; P = patient enrollment number.

Grahic Jump Location

Tables

References

Letters

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Comments

Submit a Comment
Submit a Comment

Summary for Patients

Intravenous Immunoglobulin Treatment of the Complex Regional Pain Syndrome

The summary below is from the full report titled “Intravenous Immunoglobulin Treatment of the Complex Regional Pain Syndrome. A Randomized Trial.” It is in the 2 February 2010 issue of Annals of Internal Medicine (volume 152, pages 152-158). The authors A. Goebel, A. Baranowski, K. Maurer, A. Ghiai, C. McCabe, and G. Ambler.

Read More...

Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.

Toolkit

Buy Now

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Advertisement
Related Articles
Related Point of Care
Topic Collections
PubMed Articles

Buy Now

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Forgot your password?
Enter your username and email address. We'll send you a reminder to the email address on record.
(Required)
(Required)