Logistical Issues; study never started up

Minimally invasive cardiothoracic surgery is often associated with chronic pain syndrome, out of keeping with the extent of surgical dissection. This is thought to be because of damage to the intercostal nerves by compression and traction by the surgical equipment. Cryoanalgesia is long-standing technique that freezes nerves locally to temporarily block pain sensation, which is currently used to treat acute post-operative pain in lung dissections and the Nuss procedure. We intend to perform a trial to assess whether using cryoanalgesia on intercostal nerves intraoperatively, reduces post-operative pain following minimally invasive cardiothoracic surgery.

Objective:

To characterize the effects of peri-operative intercostal cryoablation for the prevention of post thoracotomy pain following minimally invasive mitral valve surgery or atrial septal defect repair.

Rationale:

Minimally invasive cardiothoracic surgery is often associated with prolonged post-operative neuropathic pain not consistent with the acute pain experience of the initial surgery [1]. This is often thought to be secondary to an intercostal neuralgia caused by traction injuries to the intercostal neurovascular bundles by the surgical ports, a mini-thoracotomy, and mechanical retraction of the ribs.

Cryoanalgesia is an older but clinically relevant technique that causes local destruction of nerve axons using a nitrous oxide-cooled probe to -60°C [2]. This allows for temporary acute pain relief without damaging the endoneurium, allowing the peripheral nerves to regrow post-operatively. Previous studies have demonstrated cryoanalgesia as having improved acute post-operative pain vs opioids alone or similar acute pain management vs epidural analgesia [3,4]. A few studies have assessed Cryoanalgesia in thoracic surgery patients; however, these studies have focused primarily on lung operations involving pulmonary resections, and did not include cardiac operations [5,6]. Furthermore, studies that evaluated cardiothoracic operations specifically, were either retrospective or prospective in approach and did not include a representative variety of cardiac operations [7-9]. Therefore, we hope that by using intercostal cryoablation in minimally invasive cardiac surgery patients, we might improve post-operative pain and reduce analgesic requirements.

Sample Size and Statistical Considerations:

Analyses will be conducted on an intention-to-treat basis. Relative and absolute risk will be calculated with respect to the primary and secondary outcomes. We calculate a sample size of 50 patients per group in order to detect a reduction in incidence of post-thoracotomy pain from 50% to 20% (α=0.05, power=0.8). This includes an anticipated rate of non-completion of 15%.

Expected Results:

Based on our hypotheses and previous human RCT's, we expect intercostal cryoablation to improve post-thoracotomy pain when compared to controls. Furthermore, we expect an improvement in our secondary outcomes including sleep quality and analgesic requirements. Cryoanalgesia's efficacy in acute post-operative pain management is well documented in the neuropathic pain literature and has been used in a number of clinical trials. We hope that applying this concept to minimally invasive cardiothoracic procedures, we can see similar results in improved post-thoracotomy pain as reported by previous studies. We believe that, if successful, this project will offer an alternative and improved pain management regimen for patients undergoing minimally invasive thoracic surgery.

Significance:

The study proposed aims to provide new insight into the management of neuropathic pain associated with minimally invasive thoracic surgery. Pain -whether acute, chronic, nociceptive, or neuropathic- creates a significant burden to the patient, as well as to those around them. Our ultimate aim is to limit the overall pain experienced by patients. In doing this, we hope to influence a multitude of factors that affect patient welfare, including mood, patient safety, return to independence, return to work, etc. Many of these factors are often much more subjective and difficult to capture within the analytical framework of a clinical trial. However, it is our hope that by reducing pain, itself, we can continue to improve patient satisfaction and consequently, patient well-being.

Inclusion Criteria:

• Adult patients aged 18 years or older scheduled for elective minimally invasive mitral valve surgery or atrial septal defect repair.

Exclusion Criteria:

• Patients will be excluded if they are unable to fill in detailed health and pain related questionnaires, psychiatric disease preventing recall or accurate descriptions of pain, chronic pain syndromes, alcohol or illegal substance abuse, or pregnancy. Exclusion criteria also includes chronic use of opioids, allergy to morphine, bupivacaine, and/or ibuprofen, average pain during the last week >4 on a numerical rating scale from 0 to 10 with 0 indicating "no pain" and 10 indicating "the worst pain imaginable", contraindications to thoracic epidurals, prior chest surgery, or participation in another clinical trial.

Patients will be randomized to either study group before surgery without the patient's knowledge of which group they are in. The surgeons (care providers) will need to be aware of the intervention so that they can supply the cryoanalgesia or not peri-operatively. The investigator and data analyst will also be blind to the intervention type when collecting patient outcome information and doing statistical analysis. Randomization will be documented in secure password protected databases that only the surgeons will have access too, matching patient identifiers to intervention groups for reference for final data presentation.