. 2024 May 22;25(1):337.

doi: 10.1186/s13063-024-08151-4.

Prevention of persistent pain with lidocaine infusions in breast cancer surgery (PLAN): study protocol for a multicenter randomized controlled trial

James S Khan¹, Ian Gilron², P J Devereaux³, Hance Clarke^{4

5}, Nour Ayach⁶, George Tomlinson^{7

8}, May Lynn Quan⁹, Karim S Ladha^{4

10}, Stephen Choi¹¹, Allana Munro¹², Richard Brull¹³, David W Lim¹⁴, Sinziana Avramescu¹⁵, Philippe Richebé¹⁶, Nicole Hodgson¹⁷, James Paul¹⁸, Daniel I McIsaac¹⁹, Simone Derzi²⁰, Geoff L Zbitnew²¹, Alexandra M Easson²², Naveed T Siddiqui²³, Sarah J Miles²⁴, Keyvan Karkouti^{24

25}; PLAN Trial Investigators

Collaborators, Affiliations

Collaborators

PLAN Trial Investigators:
Elena Parvez, Nicole J Look Hong, Frances C Wright, Amanda Roberts, Jaime Escallon, Gary Ko, Alexander Huang, Fabricio B Zasso, Wey L Leong, Andrea M Covelli, Howard Meng, Ana Sjaus, Tina Kerelska, Vishal Uppal, Yehoshua Gleicher, Anne O'Neill, Li Wang, Daniel Sellers, Maria B C Chuquer, Geoffrey S Hawboldt, Stefan O P Hofer, Harsha Shanthanna, Lucy K Helyer, Bilal M Ansari, Salima S J Ladak, Inna Oyberman, Erin Cordeiro, Carlos A Ibarra Moreno, Elad Dana, Jason W Busse, D Norman Buckley, Siba Haykal, Stuart A McCluskey, Dolores McKeen, Julian Wiegelmann, Geoffrey Warden, Kathryn A Sparrow, Mandeep Singh, Rachael Bosma, David Flamer, Richard L Mah, Derek Diliane, Antoine Bouchard-Fortier, Alison Laws, Ashley Drohan

Affiliations

¹ Department of Anesthesiology & Pain Medicine, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada. james.khan@medportal.ca.
² Departments of Anesthesiology & Perioperative Medicine, and Biomedical & Molecular Sciences, Centre for Neuroscience Studies, and School of Policy Studies, Queen's University and Kingston Health Sciences Centre, Kingston, ON, Canada.
³ Population Health Research Institute, McMaster University, Hamilton Health Sciences Corporation, Hamilton, ON, Canada.
⁴ Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, ON, Canada.
⁵ Transitional Pain Service, Toronto General Hospital, Toronto, ON, Canada.
⁶ Department of Anesthesiology & Pain Medicine, University of Toronto, Toronto, ON, Canada.
⁷ Department of Medicine, University Health Network and Mount Sinai Hospital, Toronto, ON, Canada.
⁸ University of Toronto, Toronto, ON, Canada.
⁹ Department of Surgery/Oncology, University of Calgary, Calgary, AB, Canada.
¹⁰ Department of Anesthesia at St. Michael's Hospital, Toronto, ON, Canada.
¹¹ Department of Anesthesiology and Pain Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
¹² Department of Anesthesia, Pain Management, and Perioperative Medicine, Dalhousie University, Halifax, NS, Canada.
¹³ Department of Anesthesiology and Pain Medicine, Women's College Hospital, University of Toronto, Toronto, ON, Canada.
¹⁴ Women's College Research Institute & Department Surgery, Women's College Hospital, Toronto, ON, Canada.
¹⁵ Department of Anesthesiology and Pain Medicine, Humber River Hospital, University of Toronto, Toronto, ON, Canada.
¹⁶ Department of Anesthesiology and Pain Medicine, Maisonneuve-Rosemont Hospital, CIUSSS de L'Est de L'Ile de Montreal (CEMTL), University of Montreal, Montreal, QC, Canada.
¹⁷ Department of Surgery, McMaster University, Hamilton, ON, Canada.
¹⁸ Department of Anesthesia, McMaster University, Hamilton, ON, Canada.
¹⁹ Departments of Anesthesiology & Pain Medicine and School of Epidemiology & Public Health, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada.
²⁰ Department of Anesthesiology & Pain Medicine, University of Alberta, Edmonton, AB, Canada.
²¹ Department of Anesthesiology, Memorial University, St. John's, NF, Canada.
²² Department of Surgery and Institute of Health, Policy, Management and Evaluation (HPME), Mount Sinai Hospital and Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
²³ Department of Anesthesiology & Pain Medicine, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
²⁴ Department of Anesthesia and Pain Medicine, University of Toronto, Toronto, ON, Canada.
²⁵ Department of Anesthesia and Pain Management, University Health Network, Sinai Health System, and Women's College Hospital, Toronto, ON, Canada.

PMID: 38773653
PMCID: PMC11110187
DOI: 10.1186/s13063-024-08151-4

Prevention of persistent pain with lidocaine infusions in breast cancer surgery (PLAN): study protocol for a multicenter randomized controlled trial

James S Khan et al. Trials. 2024.

. 2024 May 22;25(1):337.

doi: 10.1186/s13063-024-08151-4.

Authors

Collaborators

PLAN Trial Investigators:
Elena Parvez, Nicole J Look Hong, Frances C Wright, Amanda Roberts, Jaime Escallon, Gary Ko, Alexander Huang, Fabricio B Zasso, Wey L Leong, Andrea M Covelli, Howard Meng, Ana Sjaus, Tina Kerelska, Vishal Uppal, Yehoshua Gleicher, Anne O'Neill, Li Wang, Daniel Sellers, Maria B C Chuquer, Geoffrey S Hawboldt, Stefan O P Hofer, Harsha Shanthanna, Lucy K Helyer, Bilal M Ansari, Salima S J Ladak, Inna Oyberman, Erin Cordeiro, Carlos A Ibarra Moreno, Elad Dana, Jason W Busse, D Norman Buckley, Siba Haykal, Stuart A McCluskey, Dolores McKeen, Julian Wiegelmann, Geoffrey Warden, Kathryn A Sparrow, Mandeep Singh, Rachael Bosma, David Flamer, Richard L Mah, Derek Diliane, Antoine Bouchard-Fortier, Alison Laws, Ashley Drohan

Affiliations

¹ Department of Anesthesiology & Pain Medicine, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada. james.khan@medportal.ca.
² Departments of Anesthesiology & Perioperative Medicine, and Biomedical & Molecular Sciences, Centre for Neuroscience Studies, and School of Policy Studies, Queen's University and Kingston Health Sciences Centre, Kingston, ON, Canada.
³ Population Health Research Institute, McMaster University, Hamilton Health Sciences Corporation, Hamilton, ON, Canada.
⁴ Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, ON, Canada.
⁵ Transitional Pain Service, Toronto General Hospital, Toronto, ON, Canada.
⁶ Department of Anesthesiology & Pain Medicine, University of Toronto, Toronto, ON, Canada.
⁷ Department of Medicine, University Health Network and Mount Sinai Hospital, Toronto, ON, Canada.
⁸ University of Toronto, Toronto, ON, Canada.
⁹ Department of Surgery/Oncology, University of Calgary, Calgary, AB, Canada.
¹⁰ Department of Anesthesia at St. Michael's Hospital, Toronto, ON, Canada.
¹¹ Department of Anesthesiology and Pain Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
¹² Department of Anesthesia, Pain Management, and Perioperative Medicine, Dalhousie University, Halifax, NS, Canada.
¹³ Department of Anesthesiology and Pain Medicine, Women's College Hospital, University of Toronto, Toronto, ON, Canada.
¹⁴ Women's College Research Institute & Department Surgery, Women's College Hospital, Toronto, ON, Canada.
¹⁵ Department of Anesthesiology and Pain Medicine, Humber River Hospital, University of Toronto, Toronto, ON, Canada.
¹⁶ Department of Anesthesiology and Pain Medicine, Maisonneuve-Rosemont Hospital, CIUSSS de L'Est de L'Ile de Montreal (CEMTL), University of Montreal, Montreal, QC, Canada.
¹⁷ Department of Surgery, McMaster University, Hamilton, ON, Canada.
¹⁸ Department of Anesthesia, McMaster University, Hamilton, ON, Canada.
¹⁹ Departments of Anesthesiology & Pain Medicine and School of Epidemiology & Public Health, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada.
²⁰ Department of Anesthesiology & Pain Medicine, University of Alberta, Edmonton, AB, Canada.
²¹ Department of Anesthesiology, Memorial University, St. John's, NF, Canada.
²² Department of Surgery and Institute of Health, Policy, Management and Evaluation (HPME), Mount Sinai Hospital and Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
²³ Department of Anesthesiology & Pain Medicine, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
²⁴ Department of Anesthesia and Pain Medicine, University of Toronto, Toronto, ON, Canada.
²⁵ Department of Anesthesia and Pain Management, University Health Network, Sinai Health System, and Women's College Hospital, Toronto, ON, Canada.

PMID: 38773653
PMCID: PMC11110187
DOI: 10.1186/s13063-024-08151-4

Abstract

Background: Persistent pain is a common yet debilitating complication after breast cancer surgery. Given the pervasive effects of this pain disorder on the patient and healthcare system, post-mastectomy pain syndrome (PMPS) is becoming a larger population health problem, especially as the prognosis and survivorship of breast cancer increases. Interventions that prevent persistent pain after breast surgery are needed to improve the quality of life of breast cancer survivors. An intraoperative intravenous lidocaine infusion has emerged as a potential intervention to decrease the incidence of PMPS. We aim to determine the definitive effects of this intervention in patients undergoing breast cancer surgery.

Methods: PLAN will be a multicenter, parallel-group, blinded, 1:1 randomized, placebo-controlled trial of 1,602 patients undergoing breast cancer surgery. Adult patients scheduled for a lumpectomy or mastectomy will be randomized to receive an intravenous 2% lidocaine bolus of 1.5 mg/kg with induction of anesthesia, followed by a 2.0 mg/kg/h infusion until the end of surgery, or placebo solution (normal saline) at the same volume. The primary outcome will be the incidence of persistent pain at 3 months. Secondary outcomes include the incidence of pain and opioid consumption at 1 h, 1-3 days, and 12 months after surgery, as well as emotional, physical, and functional parameters, and cost-effectiveness.

Discussion: This trial aims to provide definitive evidence on an intervention that could potentially prevent persistent pain after breast cancer surgery. If this trial is successful, lidocaine infusion would be integrated as standard of care in breast cancer management. This inexpensive, widely available, and easily administered intervention has the potential to reduce pain and suffering in an already afflicted patient population, decrease the substantial costs of chronic pain management, potentially decrease opioid use, and improve the quality of life in patients.

Trial registration: This trial has been registered on clinicaltrials.gov (NCT04874038, Dr. James Khan. Date of registration: May 5, 2021).

Keywords: Breast cancer surgery; Chronic pain; Chronic postsurgical pain; Lidocaine infusion; Perioperative care; Post-mastectomy pain syndrome.

PubMed Disclaimer

Conflict of interest statement

JSK—Supported by a Merit award by the Department of Anesthesiology and Pain Medicine, Recipient of a fellowship awarded by Michael G. DeGroote Institute of Pain Research and Care which supported the initial pilot for this trial.

IG—reports consulting honoraria from Combigene, GW Research, Lilly and Novaremed.

KK—Supported in part by a merit award from the Department of Anesthesia and Pain Medicine, University of Toronto-Research support and/or consultancy for Octapharma and Instrumentation Laboratory.

KSL—Co-PI of an observational study on medical cannabis funded by Shoppers Drug Mart.

DWL—Consultant with Merck Canada Inc., Speaker fees from Mayo Clinic foundation (2022).

PR—Has received several Investigator Initiated Trial grants from companies who were funders of the trials whereas my research center was the sponsor. These grants had a contract between our attorneys of our research institution and companies to make sure the PI remained totally independent form companies who were only funders (no right on data, no right on publications). Gave educational lectures for companies and received some honorarium (Medtronic, Medasense Ltd, Merck, Avirpharma).

NJLK—Consultant for MOLLI Surgical.

JWB—Supported, in part, by a Canadian Institutes of Health Research Canada Research Chair in the prevention and management of chronic pain.

MS—Currently holds the Canadian Anesthesiologists’ Society Career Scientist Grant and a Merit award from the Department of Anesthesiology and Pain Medicine, University of Toronto (Toronto, Canada) to support academic time. Dr. Singh also serves on the Medical Advisory Board of Hypersomnia Foundation (Atlanta, GA) at a voluntary basis.

PJD—Has received grant funding from the following companies: Abbott Diagnostics, Roche Diagnostics, Siemens. He has received medical devices for trials from the following company: CloudDX. He is a consultant for: Abbott Canada, Renibus, Roche Canada, Trimedic. He is a member of advisory boards to: Bayer and Quidel. He was a speaker for the following company: Velocity.

Figures

**Fig. 1**
Trial schedule of enrolment, interventions, and assessments

See this image and copyright information in PMC

References

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1. Reports H, Statistics Canada CC for HI. Canadian Cancer Statistics Advisory Committee in collaboration with the Canadian Cancer Society, Statistics Canada and the Public Health Agency of Canada. Canadian Cancer Statistics. Toronto: Canadian Cancer Society; 2021.
1. Vilholm OJ, Cold S, Rasmussen L, Sindrup SH. The postmastectomy pain syndrome: an epidemiological study on the prevalence of chronic pain after surgery for breast cancer. Br J Cancer. 2008;99(4):604–610. doi: 10.1038/sj.bjc.6604534. - DOI - PMC - PubMed
1. Jung BF, Ahrendt GM, Oaklander AL, Dworkin RH. Neuropathic pain following breast cancer surgery: proposed classification and research update. PAID. 2003;104(1–2):1–13. - PubMed
1. Schug SA, Lavand’homme P, Barke A, Korwisi B, Rief W, Treede RD, et al. The IASP classification of chronic pain for ICD-11: chronic postsurgical or posttraumatic pain. PAID. 2019;160(1):45–52. - PubMed

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Prevention of persistent pain with lidocaine infusions in breast cancer surgery (PLAN): study protocol for a multicenter randomized controlled trial

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Prevention of persistent pain with lidocaine infusions in breast cancer surgery (PLAN): study protocol for a multicenter randomized controlled trial

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Conflict of interest statement

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