Chest Tube-Delivered Bupivacaine to Decrease Postoperative Pain After Cardiac Surgery (FREEZE-B)

1. Background & Rationale Moderate to severe postoperative pain is a well-recognized complication of cardiac surgery requiring median sternotomy, including coronary artery bypass grafting (CABG). A significant contributor to this pain is the presence of pleural chest tubes, which are routinely inserted intraoperatively and remain in situ for several days postoperatively. Inadequately controlled pain following cardiac surgery is associated with impaired respiratory mechanics, reduced patient mobility, delayed recovery, increased length of stay, and heightened reliance on systemic opioid analgesics and non-steroidal anti-inflammatory drugs (NSAIDs). Opioid use, in particular, carries well-known risks including respiratory depression, nausea, constipation, urinary retention, and risk of dependence, all of which are especially problematic in the postoperative cardiac surgery population.

   Regional analgesia techniques have emerged as important adjuncts in multimodal pain management. Local anesthetic agents such as bupivacaine, delivered directly to the site of pain, offer the potential for effective, targeted analgesia without the systemic side effects of opioids. Chest tube-delivered local anesthesia is a relatively novel approach whereby the anesthetic agent is administered directly into the pleural space via the chest drainage tube, targeting the source of chest tube-related pain. Preliminary evidence and mechanistic rationale suggest that bupivacaine without epinephrine delivered in this manner may meaningfully reduce postoperative pain scores and reduce reliance on systemic analgesics, though rigorous prospective evidence from well-designed randomized controlled trials remains limited.

2. Research Question & Objectives

   Primary Research Question: Does chest tube-delivered 0.5% bupivacaine (without epinephrine), compared to normal saline placebo, reduce postoperative pain scores in patients undergoing coronary artery bypass surgery via midline sternotomy with mammary artery use?

   The primary objective is to determine whether intrapleural bupivacaine administered via chest tube significantly reduces pain intensity numeric rating scores compared to normal saline in the postoperative period following cardiac surgery.

   Secondary objectives include: (1) to evaluate the impact of chest tube-delivered bupivacaine on total postoperative analgesic consumption (opioid and NSAID doses); (2) to assess whether the intervention reduces pain at the time of pleural tube removal; (3) to evaluate the safety and tolerability of intrapleural bupivacaine in this patient population; and (4) to determine any differences in length of hospital stay or recovery milestones between groups.

3. Methods Study Design: This is a prospective, randomized, double-blind, placebo-controlled clinical trial. Eligible patients will be randomized in a 1:1 ratio to receive either chest tube-delivered bupivacaine (without epinephrine) or normal saline (placebo), administered via the pleural chest drainage tube in the postoperative period.

Population: Adult patients (≥18 years of age) undergoing elective or semi-elective coronary artery bypass surgery (CABG) via midline sternotomy involving the use of a mammary artery will be eligible for enrolment. Patients will be recruited from the cardiac surgery service at the University of Calgary / Alberta Health Services.

Intervention: Following surgery, eligible and consenting participants will be randomized to receive 10cc of 0.5% bupivacaine (without epinephrine) or 10cc normal saline administered through the pleural chest tube. The solution will be administered whenever patients report a pain equal or above 3/10 on the intensity numeric rating scale (NRS) (0 = no pain; 10 = the most intense pain) from the time of extubation, until all pleural tubes are removed. Standard postoperative analgesic protocols will be followed for both groups, and all co-interventions will be administered per standard of care. Additional doses of analgesics will be given if the NRS persists at ≥3 for more than 30 minutes post injection

Outcome Measures: The primary outcome is pain intensity as measured by a validated numeric rating scale (NRS; 0-10, where 0 = no pain and 10 = most intense pain imaginable) at pre-specified time points in the postoperative period (30, 60, 120, and 240 minutes post injection. Secondary outcomes include mean total doses of opioid analgesics and NSAIDs administered postoperatively, pain scores at time of pleural tube removal, and overall length of hospital stay.

Data Analysis: A research coordinator blinded to treatment allocation will collect all outcomes. Statistical analyses will be performed on an intention-to-treat basis. Mean pain reduction will be compared between the two groups, as well as mean total opioid and NSAIDs use.