PANDORA: Paravertebral AdjuNctive DexamethasOne Palmitate Reducing Chronic Pain After Caridiac Surgery

Effect of Continuous Paravertebral Nerve Block Combined With Dexamethasone Palmitate vs Combined With Dexamethasone Sodium Phosphate on Chronic Postoperative Pain in Patients Undergoing Minimally Invasive Cardiac Surgery

The goal of this single-center, prospective, double-blind randomized controlled clinical trial is to explore preventive interventions for chronic postoperative pain (CPSP) in patients undergoing minimally invasive cardiac surgery. The main questions it aims to answer is: the incidence of CPSP is high and severe, and there is no safe and effective method for prevention and treatment. The participants in the dexamethasone palmitate (DXP) group will receive a single paravertebral space infusion of 21 ml of the first dose of analgesia, consisting of 0.5 percentage ropivacaine 20 ml and dexamethasone palmitate 1ml. The participants in dexamethasone sodium phosphate (DXM) group will receive a single infusion of a paravertebral space first dose of 21 ml of analgesic containing 0.5 percentage ropivacaine 20 ml and dexamethasone sodium phosphate 1ml. Then both groups use a continuous paravertebral nerve block pump for postoperative analgesia. The liquid of the pump is 250 ml 0.2 percentage ropivacaine. The background of the pump is set to 5 ml/h and PCA is set to 5 ml at an interval of 30 min.

Study Overview

• Status: Completed
• Conditions: Chronic Postoperative Pain
• Intervention / Treatment: Drug: Dexamethasone Palmitate; Drug: Dexamethasone Sodium Phosphate

Detailed Description

Minimally invasive cardiac surgery has the advantages of small injury, rapid recovery and international leadership. But the incidence of chronic pain after operation is high, which is reported to be as high as 70 percentage in thoracic intercostal surgery, seriously affecting the quality of life of patients after surgery. Uncontrolled acute pain after surgery poses the greatest risk factor for CPSP. Procedure-specific postoperative pain management (PROSPECT) guidelines recommend that the use of paravertebral nerve block as the first choice for multimodal analgesia in intercostal surgery can significantly reduce the incidence of postoperative acute pain. But there is not enough evidence to prove that it can reduce the incidence of CPSP. Choosing a reasonable combination of analgesics in nerve block to inhibit the production and transmission of multi-source nociceptive signals caused by intercostal nerve injury and inflammatory stimulation is one of the research hotspots to prevent the transformation from acute pain to chronic pain.

Dexamethasone can play an anti-inflammatory effect by reducing the sensitivity caused by neuroinflammation, which has also been confirmed by small sample studies. But a large number of literatures point out that a single use of dexamethasone cannot significantly reduce the incidence of CPSP. This may be due to the fact that the half-life of dexamethasone is only 48 hours, and single use is not enough to exert anti-inflammatory effects; long-term large-scale use can increase blood sugar concentration, leading to complications such as poor wound healing. From this, the investigators infer that finding a means or preparation to prolong the action time and efficacy of dexamethasone while reducing side effects may become an important means of preventing CPSP.

Dexamethasone palmitate is a kind of dexamethasone nanoparticles with long curative effect, good effect and few side effects. It plays a very significant therapeutic role in the late stage of inflammation and has been proved to prevent the progression of inflammation. And there have been studies on the injection of dexamethasone palmitate in epidural or perineural space, but the safety and efficacy of dexamethasone palmitate in paravertebral space need to be further studied.

The primary aim of this study is to compare whether single injection of dexamethasone palmitate and dexamethasone sodium phosphate around the paravertebral nerve combined with continuous paravertebral nerve block for postoperative analgesia can reduce the incidence of chronic pain 3 months after operation.

• Study Type: Interventional
• Enrollment (Actual): 562
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Xi'an, China, 710032
    • Xijing Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. NYHA class I-III
2. 18 years to 65 years
3. Undergoing intercostal incision cardiac surgery

Exclusion Criteria:

1. Urgent surgery
2. BMI≧35kg/m^2
3. Non-first cardiac surgery
4. Local anesthetic allergy
5. Skin damage or infection at the puncture site
6. Dysfunction of liver, kidney and blood coagulation
7. Previously had chronic pains

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DXP group; The participants in DXP group will receive a first dose of a single paravertebral space infusion of 21 ml of analgesic containing 0.5 percentage ropivacaine 20 ml and dexamethasone palmitate 1ml.	Drug: Dexamethasone Palmitate; a single paraverteal space infusion of 21 ml of the first dose of analgesia, consisting of 0.5 percentage ropivacaine 20 ml and dexamethasone palmitate 1ml. Then, a continuous paraverteal nerve block pump was connected for postoperative analgesia. The liquid of the pump was 250 ml 0.2 percentage ropivacaine. The background of the pump was set to 5 ml/h and PCA was set to 5 ml at an interval of 30 min.
Active Comparator: DXM group; The participants in DXM group will receive a single infusion of a paravertebral space first dose of 21 ml of analgesic containing 0.5 percentage ropivacaine 20 ml and dexamethasone sodium phosphate 1ml.	Drug: Dexamethasone Sodium Phosphate; a single paraverteal space infusion of 21 ml of the first dose of analgesia, consisting of 0.5 percentage ropivacaine 20 ml and dexamethasone sodium phosphate 1ml. Then, a continuous paraverteal nerve block pump was connected for postoperative analgesia. The liquid of the pump was 250 ml 0.2 percentage ropivacaine. The background of the pump was set to 5 ml/h and PCA was set to 5 ml at an interval of 30 min.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of chronic postoperative pain	Pain status score on the Brief Pain Inventory（BPI-NRS score range, 0-10; ≥1 indicates it happens）	3 months after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morphine consumption	Total consumption of rescue analgesia by oral morphine equivalent (mcg/kg)	24, 48, 72 hours after surgery
The incidence of acute pain at resting and activity	Numerical Rating Scale to evaluate the incidence of pain (NRS score range, 0-10; ≥1 indicates it happens once)	24, 48, 72 hours after surgery
The incidence of chronic postoperative pain	Pain status score on the Brief Pain Inventory（BPI-NRS score range, 0-10; ≥1 indicates it happens）	6 and 12 months after surgery
Pain severity in the past 7 days	Patient-Reported Outcomes Measurement Information System (PROMIS) Scale v2.0 - Pain Intensity 3a (T-score range, 36.3-81.8; 81.8 indicates worst pain intensity)	3, 6, 12 months after surgery
Pain severity in the past 24 hours	Brief Pain Inventory (BPI pain intensity score rang, 0-40; 40 indicates worst pain intensity)	3, 6, 12 months after surgery
The interference of chronic postoperative pain on activities of daily living in the past 7 days	PROMIS Short Form v1.1 - Pain Interference 8a (PROMIS-PI-SF-8A; T-score range, 40.7-77; 77 indicates worst pain interference)	3, 6, 12 months after surgery
The interference of chronic postoperative pain on activities of daily living in the past 24 hours	Brief Pain Inventory (BPI pain interference score rang 0-70; 70 indicates worst pain interference)	3, 6, 12 months after surgery
The impact of chronic postoperative pain on neuropathic pain	PROMIS Scale v2.0 - Neuropathic Pain Quality 5a (T-score range, 37.0-74.1; 74.1 indicates highly neuropathic pain)	3, 6, 12 months after surgery
The impact of chronic postoperative pain on health related quality of life	12-item Short-Form Health Survey v2 (SF-12 v2.0 scores range, 0-100, 100 indicates best functioning)	3, 6, 12 months after surgery
The impact of chronic postoperative pain on sleep quality	Pittsburgh Sleep Quality Index (PSQI score range, 0-21, 21 indicates worst sleep quality)	3, 6, 12 months after surgery
The impact of chronic postoperative pain on emotional wellbeing	Hospital Anxiety and Depression Scale (HADS score range, 0-21, 21 indicates worst anxiety or depression)	3, 6, 12 months after surgery
The impact of chronic postoperative pain on self-efficacy	Pain Self Efficacy Questionnaire (PSEQ score range, 0-60, 60 indicates strongest self-belief)	3, 6, 12 months after surgery

Collaborators and Investigators

• Sponsor: Xijing Hospital
• Investigators: Principal Investigator: Chong Lei, MD&phD, Xijing Hospital; Principal Investigator: Taoyuan Zhang, M.D., Xijing Hospital

Publications and helpful links

General Publications

• Zhang H, Zhang T, Zheng Z, Gao J, Gao B, Hou L, Zhao J, Wang L, Dong H, Lei C. Rationale and design for the thoracic Paravertebral Adjunctive Dexamethasone Palmitate Reducing chronic pain After cardiac surgery (PANDORA) trial: a parallel-group, double-blinded, randomised controlled, single-centre study. BMJ Open. 2025 Jan 15;15(1):e086392. doi: 10.1136/bmjopen-2024-086392.

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2023
• Primary Completion (Actual): September 18, 2024
• Study Completion (Actual): October 30, 2025

Study Registration Dates

• First Submitted: June 15, 2023
• First Submitted That Met QC Criteria: June 24, 2023
• First Posted (Actual): June 27, 2023

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain, Postoperative; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Enzyme Inhibitors; dexamethasone 21-phosphate; dexamethasone 21-palmitate
• Other Study ID Numbers: KY20232194-C-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No