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

James S Khan; Ian Gilron; P J Devereaux; Hance Clarke; Nour Ayach; George Tomlinson; May Lynn Quan; Karim S Ladha; Stephen Choi; Allana Munro; Richard Brull; David W Lim; Sinziana Avramescu; Philippe Richebé; Nicole Hodgson; James Paul; Daniel I McIsaac; Simone Derzi; Geoff L Zbitnew; Alexandra M Easson; Naveed T Siddiqui; Sarah J Miles; Keyvan Karkouti; PLAN Trial Investigators

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

Trials. 2024 May 22;25(1):337. doi: 10.1186/s13063-024-08151-4.

Authors

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

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.

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.

Publication types

Clinical Trial Protocol

MeSH terms

Analgesics, Opioid / administration & dosage
Analgesics, Opioid / adverse effects
Analgesics, Opioid / therapeutic use
Anesthetics, Local* / administration & dosage
Anesthetics, Local* / adverse effects
Breast Neoplasms* / surgery
Chronic Pain / etiology
Chronic Pain / prevention & control
Cost-Benefit Analysis
Female
Humans
Infusions, Intravenous
Lidocaine* / administration & dosage
Lidocaine* / adverse effects
Mastectomy* / adverse effects
Mastectomy, Segmental / adverse effects
Multicenter Studies as Topic*
Pain Measurement
Pain, Postoperative* / diagnosis
Pain, Postoperative* / etiology
Pain, Postoperative* / prevention & control
Quality of Life
Randomized Controlled Trials as Topic*
Time Factors
Treatment Outcome

Associated data

ClinicalTrials.gov/NCT04874038

Abstract

Publication types

MeSH terms

Associated data

Grants and funding