top of page

MINS Substudy


Myocardial injury after noncardiac surgery (MINS) is the most common perioperative cardiovascular complication affecting up to 8 million adults worldwide annually. Patients who suffer MINS are at increased risk of postoperative mortality and major non-fatal cardiovascular complications with this elevated risk persisting well beyond the early postoperative period. The perioperative physiological and pathophysiological processes that are thought to contribute to the myocardial ischaemia that result in MINS include the perioperative stress response, haemodynamic instability, bleeding and clotting disturbances. These interrelated processes represent potential avenues for the treatment or prevention of MINS.


Lidocaine is an amide local anaesthetic in widespread use worldwide. When administered intravenously, lidocaine has a wide therapeutic margin and its safety is well supported. In addition to its recognised analgesic and antiarrhythmic properties it has been shown to exert pleiotropic anti-inflammatory effects as well as cardioprotective effects against myocardial ischaemia and reperfusion injury.


A substudy of 105 patients in the VAPOR-C Feasibility Study compared patients who received intravenous lidocaine administered at a dose greater than during major cancer surgery to those that did not. This small unrandomised sample showed a significant reduction in MINS and markers of inflammation in patients that received lidocaine when compared to those that did not. This supports the plausibility that perioperative inflammation is implicated in the pathogenesis of MINS and that lidocaine may have a role in reducing the incidence of MINS.


The VAPOR-C Trial provides the optimal environment in which to study the impact of lidocaine on MINS in a randomised control trial. The MINS in VAPOR-C Trial will be run as a sub-study of the main VAPOR-C Trial at participating sites.

  • Status
  • Design
    This is an event-driven, randomised control trial with a 2x2 factorial design. Subjects are randomised in the ratio of 1:1:1:1 using permuted block randomisation stratified by cancer type and by treating centre to receive either 1) sevoflurane maintenance anaesthesia and lidocaine infusion or 2) sevoflurane maintenance anaesthesia; or 3), propofol maintenance anaesthesia and lidocaine infusion or 4), propofol maintenance.
  • Primary Objectives
    1. To determine if propofol-TIVA increases Disease Free Survival (DFS) compared with sevoflurane 2. To determine if intravenous lidocaine increases DFS compared with no lidocaine
  • Secondary Objectives
    The secondary objectives for this study are: To compare propofol-TIVA versus sevoflurane in regards to: Overall Survival Days Alive and out of Hospital at 30 days To compare intravenous lidocaine versus no lidocaine in regards to: Overall Survival Chronic Post Surgical Pain at 90 days Days Alive and out of Hospital at 30 days To compare propofol-TIVA versus sevoflurane as well as intravenous lidocaine versus no lidocaine in regard to: Post-operative complications Functional capacity Acute post-operative pain Chronic post-surgical pain (at 90 days and 12 months) Adverse events during surgery until discharge from Post Anaesthetic Care Unit (PACU) or to within the first 4 hours of intensive care unit (ICU) admission Health utility
  • Population
    We expect to recruit 3,500 subjects across approximately 40 sites.
  • Eligibility Criteria
    Key Eligibility criteria Male or female patients aged 18 years or older Patients with Stage I-III colorectal cancer or Stage I-IIIa non-small cell lung carcinoma Patients receiving elective, surgical resection with curative intent Surgery expected to last ≥2 hours and expected to require ≥2 nights hospital stay
  • Duration
    Planned recruitment duration is 4 years and patients will be followed up every year after surgery for up to three years. The expected total study duration is up to 7 years.
  • VAPOR-C Feasibility Study
    In preparation for this large, international RCT, we undertook a randomised, double-blinded, feasibility and pilot study of propofol-TIVA or volatile-based maintenance anaesthesia during cancer resection surgery at four tertiary hospitals in Australia and the United States. Patients were randomised on day of surgery to receive either TIVA or volatile-based maintenance anaesthesia. We demonstrated feasibility of the study protocol with a recruitment rate of 67% and a 99% adherence to randomised treatment. . As part of this feasibility study, exploratory sub-studies were undertaken to further investigate the impact of anaesthetic technique on perioperative stress response and postoperative outcome and a biorepository of over 450 patient blood samples was established from colorectal, lung, prostate, melanoma and breast cancer surgical patients. Novel work is being undertaken in in collaboration with senior scientists across the University of Melbourne (Professor Fred Hollande) and Monash University (A/Professor Erica Sloan) to interrogate the inflammatory-immune response to anaesthesia and the potential impact of surgery on tumour cell proliferation and metastasis. . The feasibility and pre-clinical studies were developed and completed with the assistance and support of: MCATS and The University of Melbourne ANZCA and ANZCA CTN Monash University Drug Discovery Biology Peter MacCallum Cancer Centre Victorian Comprehensive Cancer Centre (VCCC)
  • Funding Body Acknowledgments
    This study has been funded by grants and in-kind support from the following: National Health and Medical Research Council Victorian Comprehensive Cancer Centre The University of Melbourne Australian and New Zealand College of Anaesthetists
bottom of page