EFFICACY AND SAFETY OF PULSED RADIOFREQUENCY TREATMENT IN CHRONIC PAIN SYNDROMES Introdução à Medicina II | Teacher Luís Filipe Azevedo | Class 14

Summary Introdução à Medicina II | Teacher Luís Azevedo | Class 14 1.Introduction 2.Methods 3.Results 4.Discussion 5.Conclusion 6.Website 7.References

1.Introduction Research question and aims What is the efficacy and safety of Pulsed Radiofrequency treatment in chronic pain syndromes? Aim: To systematically review the evidence about efficacy and safety of pulsed radiofrequency in patients with chronic pain syndromes. Introdução à Medicina II | Teacher Luís Azevedo | Class 14

1.Introduction What is pain? PAINPAIN Acute Chronic The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage." [1] Introdução à Medicina II | Teacher Luís Azevedo | Class 14 [1] Abu-Saad Huijer H. Chronic pain: a review. J Med Liban 2010 Jan-Mar;58(1):21-7

1.Introduction Introdução à Medicina II | Teacher Luís Azevedo | Class 14 [2] Van Zundert J, Huntoon M, Patijn J, Lataster A, Mekhail N, van Kleef M. Cervical Radicular Pain. Pain Pract Oct 5.4 Different treatments for chronic pain [2]

Radiofrequency treatment [3] 1.Introduction Introdução à Medicina II | Teacher Luís Azevedo | Class 14 [3] Byrd D, Mackey S. Pulsed radiofrequency for chronic pain. Curr Pain Headache Rep Jan;12(1):37-41 Is a recently developed treatment modality for pain syndromes such as chronic pain. It uses brief pulses of high voltage to produce controlled tissue destruction, reducing pain by modulating its transmission. Importance of this treatment Its apparent lack of side effects which is appealing for those who suffer from chronic pain which has detrimental effects on physical and mental health. [1]

Project Development Phases 1.Research question formulation 2.Definition of selection criteria (inclusion and exclusion) 3.Definition and implementation of literature search methods and resources 4.Study selection using defined selection criteria 5.Data extraction from included studies 6.Critical appraisal and quality assessment of included studies 7.Data analysis and synthesis from included primary studies 8.Writing and disseminating final report 2. Methods Introdução à Medicina II | Teacher Luís Azevedo | Class 14

 Type of study Systematic Review  Units of analysis Articles  Data Search PubMed ISI Web of Knowledge Scopus Central 2. Methods Introdução à Medicina II | Teacher Luís Azevedo | Class 14

 Key-words Pain Chronic Pulsed Radiofrequency  Query PubMed: pulsed[All Fields] AND radiofrequency[All Fields] AND (("pain"[MeSH Terms] OR "pain"[All Fields]) AND chronic[All Fields]) Scopus: TITLE-ABS-KEY(radiofrequency) AND TITLE-ABS-KEY(pulsed) AND TITLE-ABS-KEY(pain) AND TITLE-ABS- KEY(chronic) ISI TS=(Radiofrequency SAME pulsed) AND TS=pain AND TS=chronic Central #1 MeSH descriptor Pain explode all trees #2 (Chronic): ti, ab, kw #3 (Radiofrequency Near Pulsed): ti, ab, kw 2. Methods  MeSH Term: Pain Introdução à Medicina II | Teacher Luís Azevedo | Class 14

 Research Limits 2. Methods Inclusion CriteriaExclusion Criteria 1. Articles that mention the radiofrequency treatment in chronic pain 1. Theme does not match the expected 2. Articles that have, at least, two comparative groups 2. Treatment is not used for chronic pain 3. Articles that mention the issue of efficacy and safety of pulsed radiofrequency 3. Type of article is not the desired 4. Study is not conducted in humans 5. Article does not mention the methods used and results Introdução à Medicina II | Teacher Luís Azevedo | Class 14

2. Methods Articles found 78 PUBMED 48 ISI Web 32 SCOPUS 65 CENTRAL 3 65 excluded 13 included Introdução à Medicina II | Teacher Luís Azevedo | Class 14 5 included articles 2nd selection stage

3. Results Articles Excluded Exclusion CriteriaArticles 1. Theme does not match the expected 2 2. Treatment is not used for chronic pain 1 3. Type of article is not the desired Study is not conducted in humans3 5. Article does not mention the methods used and results0 Introdução à Medicina II | Teacher Luís Azevedo | Class 14

3. Results Articles Excluded Exclusion CriteriaArticles 1. Theme does not match the expected 2 2. Treatment is not used for chronic pain 1 3. Type of article is not the desired Study is not conducted in humans3 5. Article does not mention the methods used and results0 Introdução à Medicina II | Teacher Luís Azevedo | Class 14

3. Results Introdução à Medicina II | Teacher Luís Azevedo | Class 14 Publication year

3. Results Introdução à Medicina II | Teacher Luís Azevedo | Class 14 Inclusion/Exclusion: 8 disagreements Reason for exclusion: 4 disagreements Agreement / Disagreement

3. Results Included Articles: Study and Methods Patients and treatments Results Study limitations Number of patients in each group Setting Adverse reactions or events Van Zundert et al Prospective, randomised, sham-controlled, double blind trial 23 patients with cervical radicular syndrome, PRF of DRG compared with sham intervention 3 months follow- up: PRF group with better outcome – GPE and VAS (20%) Only 23 patients, short-term follow up, high pre- treatment VAS of sham treated group 11 patients – PRF group; 12 patients – sham treated group Netherland - Cohen et al, Retrospective data analysis 49 patients with post surgical thoracic pain, PRF of DRG and PRF of ICN compared with pharmacotherapy Both 6 weeks and 3 months follow up: PRF of DRG group with better outcome Retrospective, Only 49 patients, short- term maximum follow up (3 months) PRF of DRG (n=13) PRF of ICN (n=15) Pharmacotherapy (n=21) USA Only in the pharmacotherapy group, 7 of the 21 patients revealed adverse side effects

3. Results Included Articles: Study and Methods Patients and treatments Results Study limitations Number of patients in each group Setting Adverse reactions or events Simopoulos et al Prospective, randomised, sham-controlled, double blind trial 76 patients with chronic lombo- sacral pain randomly assigned to one of two types of treatment: PRF of the DRG or PRF followed by continued radiofrequency. 2 months follow up: success (2 groups); non statistically difference between the two treatment groups. The efficacy of PRF is not tested on the comparative group 37 - PRF 39 - PRF followed by continues radiofrequency USA Israel - Lindner et al. Retrospective study 48 patients with low back pain and >50% pain relief following a diagnostic medial branch block.: PRF treatment of the medial branch 21/29 nonoperated patients and 5/19 operated patients, successful outcome. The setup of our study does not permit a comparison with the results of continuous radiofrequency (CRF) for the same procedure 19 patients operated 29 patients non- operated Switzerland -

3. Results Included Articles: Study and Methods Patients and treatments Results Study limitations Number of patients in each group Setting Adverse reactions or events Tekin I et al Prospective, randomized, double-blind, sham lesion controlled trial 60 patients with continuous low back pain with no radicular syndrome. 80ºC CRF compared to 2Hz PRF and to local anesthetic. VAS and ODI scores of PRF and CRF groups were lower than the control group. In the follow up period the scores were lower in the CRF group than those of the PRF. Risk of ending the blinding process after 3 month follow-up. Few support studies. Risk of false positive blocks 20 patients- Control Group 20 patients- PRF Group 20 patients- CRF Group Turkey -

3. Results Quantitative results: VAS – Visual Analogue Scale VAS Control or alternative intervention group VAS PRF group ArticleIntervention Primary outcome Secondary outcome Intervention Primary outcome Secondary outcome Cohen et al, 2006 Medical management group 6 weeks: 27.3% reported ≥ 50% pain relief 3 months: 19.9% reported ≥ 50% pain relief PRF group 6 weeks: 61.5% reported ≥ 50% pain relief 3 months: 53.8% reported ≥ 50% pain relief Lindner et al, 2006 Operated patients 1 month: - 4 months: 5/19 reported ≥ 60% pain relief Nonoperated patients 1 months: - 4 months: 21/29 reported ≥ 60% pain relief Van Zundert et al, 2007 Sham group: 76,2 3 months: 3/12 (25%) improvement 6 months: < improvement PRF group: 55,7 3 months: 9/11 (82%) improvement 6 months: > improvement Tekin et al, 2007 Control group: Similar 6 months: Higher 1 year: Similar PRF group: Similar 6 months: Lower 1 year: Similar Simopoulos et al, 2008 PRF + CRF group: 7.1 ± weeks: 2.3 ± PRF group: 7.8 ± weeks: 3.5 ± 3.4 -

3. Results Checklist for randomized controlled trials CONSORT checklist

3. Results Checklist for observational studies STROBE checklist

3. Results ArticleChecklist evaluation Van Zundert et al, % Lindner et al, ,75% Cohen et al, % Tekin et al, ,25% Simopoulos et al, ,75%

3. Results Side-effects and complications of PRF: Although a potential for bleeding, nerve damage, infection and burns from incorrect needle or grounding pad placement have been suggested [4], none of the studies reviewed reported any noticeable complications of PRF application. [4] Cohen S, Foster A. Pulsed radiofrequency as treatment for groin pain and orchialgia. Urology. 2003, 61:645

4. Discussion The majority of the clinical studies of PRF reported its clinical efficacy. There are many articles about PRF, which report small un-controlled prospective trials, retrospective studies with only one group or reviews. The articles refer almost uniform beneficial effects of PRF. It is possible that therapeutic failures with PRF were not reported. The randomized, controlled clinical data available on PRF is limited and the articles about them are recent. There probably exists a significant margin of safety because no neurological deficits were found in patients treated with PRF and CRF. [5] [5] Simopoulos TT, Kraemer J, Nagda JV, Aner M, Bajwa ZH; Pain Physician; 2008

5. Conclusion The controlled clinical data on pulsed radiofrequency is limited and provide a level 2 or 3 of evidence of its efficacy. Despite the weakness of the controlled clinical data, the apparent lack of complications and the wider applicability of PRF call for further RCTs. … in order to achieve a clear understanding about PRF’s role in the treatment of different and various chronic pain syndromes.

6. Website

7. References Introdução à Medicina II | Teacher Luís Azevedo | Class 14 [1] Abu-Saad H. Chronic pain: a review. J Med Liban. 2010; 58(1):21-7 [2] Van Zundert J, Huntoon M, Patijn J, Lataster A, Mekhail N, van Kleef M. Cervical Radicular Pain. Pain Pract Oct 5.4 [3] Byrd D, Mackey S. Pulsed radiofrequency for chronic pain. Curr Pain Headache Rep Jan;12(1): [4] Cohen S, Foster A. Pulsed radiofrequency as treatment for groin pain and orchialgia. Urology. 2003, 61:645 [5] Simopoulos TT, Kraemer J, Nagda JV, Aner M, Bajwa ZH; Response to pulsed and continuous radiofrequency lesioning of the dorsal root ganglion and segmental nerves in patients with chronic lumbar radicular pain; Pain Physician; 2008;11(2): [6] Sackett DL, Strauss SE, Richardson WS, et al. Evidence-Based Medicine: How to Practice and Teach EBM. Philadelphia, Pa: Churchill- Livingstone; [7] Malik K. Pulsed radiofrequency: a critical review of its efficacy. Anaesthesia and Intensive Care; 2007; 35:6 [8] Green, S. Systematic reviews and meta-analysis; Singapore Med J. 2005; 46: 270 [9] Moher, D., Schulz, KF., Altman, DG.; CONSORT Group. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomised trials. Clin Oral Investig 2003; 7:2–7 [10] Bidstrup, B. Who Reviews the Reviewers?. Asian Cardiovasc Thorac Ann. 2006; 14: [11] Jadad, A.R., Moore, R.A., Carroll, D., Jenkinson, C., Reynolds, D.J.M., Gavaghan, D.J., Carroll, D.C., McQuay, H.J. Assessing the quality of reports of randomized clinical trials: is blinding necessary?. Contr Clin Trials. 1996; 17:1-12 [12] von Elm, E., Altman, D., Egger, M., Pocock, S., Gøtzsche, P., Vandenbroucke, J.; STROBE Initiative. Strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. BMJ. 2007; 335: [13] Gan, W., Man, S., Senthilselvan, A., Sin, D. Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis. Thorax. 2004; 59: