Effect of intraoperative magnesium on the incidence of chronic post surgical pain after thoracotomy

Chronic post surgical pain (CPSP) is a recognised and adverse outcome of many surgical procedures. It was first reported by Macrae and Davis and is defined as “pain persisting for at least two months duration following a surgical procedure”. Other causes for the pain and the possibility that the pain is from a pre-existing condition should be excluded before classifying the pain as CPSP. The prevalence of CPSP varies depending on the operation with higher rates observed after major thoracic surgery. In fact, patients undergoing thoracotomy have one of the greatest incidences of CPSP among all surgical procedures. The etiology of chronic post-thoracotomy pain is not understood fully. It is thought to result from potential intercostal nerve damage. As there is also a component of neuropathic pain, rather than inflammatory or nociceptive pain, central sensitisation is likely involved. Central sensitisation relies on N-methyl-D-aspartate (NMDA) receptor activation by excitatory neurotransmitters, such as glutamate and aspartate. Studies have shown that NMDA receptor antagonists, such as ketamine, can decrease CPSP. In theory, magnesium, which is a physiologic antagonist of NMDA receptors, should prevent central sensitisation and therefore reduce the incidence of CPSP. The aim of this study is to investigate the effects of intraoperative systemic magnesium on chronic postsurgical pain in patients undergoing thoracotomy. We propose to perform a single centre, prospective, double-blind, placebo-controlled study over the period of one year. Our hypothesis is that intra-operative systemic administration of magnesium will reduce the incidence of CPSP in patients undergoing thoracotomy. On the morning of surgery, block randomisation and sealed envelope method will be used to assign patients to one of the two groups: magnesium group or control group. The anaesthetist, surgeon, patient and those assessing outcomes will be blinded to the group assignment. A bolus dose of 50mg/kg of magnesium (magnesium sulfate) will be administered for 15 minutes immediately after induction and prior to skin incision, followed by infusion at 10mg/kg/hr. Patients in the control group will be administered the same volume of isotonic saline. Patients will be assessed on postoperative day 1 and 2 by a pain team (includes anaesthetist and pain nurse). A 0-10 point numeric rating scale (NRS) will be used to measure the degree of pain intensity. Higher scores indicate a higher degree of pain. Postoperative opioid consumption (24 hours and 48 hours) will also be recorded by converting to the equivalent dose of intravenous morphine. Patients will be assessed at 2 and 6 months post surgery. This will be done via a telephone call from a pain nurse. Patients reporting pain will be asked to present to a chronic pain clinic for assessment by an anaesthetist. All patients will be asked to complete a Medical Outcome Study 36-Item Short Form to assess health related quality of life.