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

A Randomized Double-Blind Placebo Controlled Trial for Chest Tube-Delivered Bupivacaine to Decrease Postoperative Pain After Cardiac Surgery: the FREEZE-B Trial

Background:

After heart surgery, patients require temporary chest tubes - plastic drains placed inside the chest to prevent fluid building up around the heart and lungs. These tubes are often very painful and can limit breathing, coughing, and movement, which necessitates usage of painkiller medication (opioids and non-steroidal anti-inflammatory drugs (NSAIDs)) that have negative side effects and can prolong hospital recovery. Despite this common problem, routine care lacks simple, add-on strategies that directly numb pain at the chest tube sites rather than relying solely on whole-body painkiller medicine.

Purpose:

To determine whether injecting a long-acting numbing medicine (bupivacaine 0.5%) through chest tubes safely reduces pain and lowers opioid and NSAID use compared with placebo.

Objective:

With ethics approval, data access, and study procedures already in place before May, the specific objective for this studentship is to collect and analyze data to evaluate the short-term effect of bupivacaine versus placebo on:

• Mean pain scores from initial recovery to chest tube removal
• Total mean opioid and NSAID use

Methods:

This single-centre, 1:1 block randomized, double-blind, placebo-controlled trial will enroll 60 adults undergoing coronary artery bypass (procedure to bypass blocked blood vessels supplying heart muscle using healthy blood vessels) at the Foothills Medical Centre. Patients receive either 10 mL bupivacaine 0.5% or normal saline (saltwater placebo) through chest tubes by heart surgeons whenever pain hits ≥3/10 using the Numeric Rating Scale (0 = no pain; 10 = most intense pain), from initial recovery to chest tube removal. Standard pain care will continue for all patients. The study team will record pain scores, opioid and NSAID doses, and any side effects for each group. Interval pain reduction will be measured 30, 60, 120 and 240 minutes post injection. Mean pain reduction and total painkiller use will be compared between the two groups.

Study Overview

• Status: Not yet recruiting
• Conditions: Chest Tubes; Post Operative Pain Control; Coronary Artery Bypass Graft (CABG)
• Intervention / Treatment: Drug: 10cc injection of normal saline (0.9%); Drug: 0.5% Bupivacaine without epinephrine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Corey Adams, MD; Phone Number: 403-944-6557; Email: corey.adams@albertahealthservices.ca
• Study Contact Backup: Name: Brandon Pentz, MSc; Email: Brandon.Pentz@ucalgary.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18 years or older at the time of consent
• Scheduled to undergo elective or semi-elective coronary artery bypass graft (CABG) surgery via midline sternotomy
• Procedure involves the use of a mammary artery graft
• Capable of providing informed written consent prior to surgery
• Able to communicate pain scores using a numeric rating scale (NRS)

These criteria ensure the study population is the clinically relevant group most likely to benefit from the intervention and that participants can provide valid consent and meaningful pain assessments.

Exclusion Criteria:

• Known allergy or hypersensitivity to bupivacaine or any amide-type local anesthetic
• Emergency or urgent cardiac surgery where obtaining consent prior to the procedure is not feasible
• Inability to communicate pain using numeric rating scale due to cognitive impairment, language barrier, or altered level of consciousness
• Participation in another interventional clinical trial that may confound pain outcome

These exclusion criteria are designed to protect participant safety, ensure the validity and interpretability of study outcomes (pain scoring ability), and maintain scientific rigor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 0.9% Saline (Placebo); 10cc injection of normal saline (0.9%)	Drug: 10cc injection of normal saline (0.9%); 10cc injection of normal saline (0.9%) through pleural chest tubes
Experimental: 0.5% Bupivacaine group (intervention); 10cc injection Bupivacaine 0.5% without epinephrine	Drug: 0.5% Bupivacaine without epinephrine; Injection of 10cc 0.5% Bupivacaine without epinephrine through pleural chest tubes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain intensity	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 starting from extubation in the CVICU.	The solution will be administered whenever patients report a pain equal or above 3/10 on the intensity numeric rating scale (NRS) and pain will be measured at 30, 60, 120, and 240 minutes after study solution injection during the postoperative period.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative postoperative opioid analgesic and NSAID consumption in postoperative period	Mean total doses of opioid analgesics and NSAIDs administered postoperatively	From extubation in the CVICU until discharge from the cardiovascular intensive care unit (CVICU), up to 7 days postoperatively.
Length of hospital stay	Length of stay in the intensive care unit (ICU) and total hospital length of stay	From hospital admission until CVICU discharge and from hospital admission until hospital discharge, respectively (up to 30 days postoperatively).

Collaborators and Investigators

• Sponsor: University of Calgary

Study record dates

Study Major Dates

• Study Start (Estimated): June 15, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: June 2, 2026
• First Submitted That Met QC Criteria: June 8, 2026
• First Posted (Actual): June 11, 2026

Study Record Updates

• Last Update Posted (Actual): June 11, 2026
• Last Update Submitted That Met QC Criteria: June 8, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Anilides; Amides; Aniline Compounds; Amines; Catechols; Phenols; Benzene Derivatives; Alcohols; Amino Alcohols; Ethanolamines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Bupivacaine; Epinephrine
• Other Study ID Numbers: REB26-0191

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: At the time of trial registration, a final decision regarding the sharing of individual participant data (IPD) has not been made. Any future data-sharing plans will be evaluated following study completion and will take into consideration participant confidentiality, institutional policies, ethical approvals, applicable regulations, and the scientific value of data sharing.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No