CROPS Study: Chronification of Post-Surgical Pain and Risk Assessment (CROPS)

Chronification of Post-Surgical Pain and Validation of a Novel Risk Assessment Tool: A Prospective Multicenter Randomized Controlled Trial

Chronic post-surgical pain (CPSP) represents a major clinical problem associated with impaired functional recovery, reduced quality of life, prolonged opioid use, and increased healthcare utilization. The mechanisms underlying pain chronification are multifactorial and involve complex interactions among surgical trauma, inflammatory responses, central sensitization, neuroimmune activation, and psychosocial risk factors.

The CROPS study (Chronification of Post-Surgical Pain and Risk Assessment) is a prospective multicenter randomized controlled trial designed to evaluate the impact of perioperative analgesic strategies on the development of chronic post-surgical pain and to validate a novel questionnaire-based pain chronification risk assessment tool in adult patients undergoing cardiac surgery.

Participants will be randomized to receive either standard multimodal opioid-based perioperative analgesia or regional anesthesia-based perioperative analgesia incorporating chest wall plane block techniques, including erector spinae plane block, paravertebral block, or PECS block, according to institutional practice.

The study will compare postoperative pain intensity, opioid consumption, postoperative recovery, postoperative complications, health-related quality of life, and the incidence of chronic post-surgical pain at 3 months after surgery. In parallel, the predictive performance of the pain chronification risk assessment questionnaire will be evaluated using discrimination and calibration analyses.

The study is conducted as an investigator-initiated academic collaboration between the East Slovakia Institute of Cardiovascular Diseases, Košice, Slovakia, and Uppsala University Hospital, Uppsala, Sweden.

Study Overview

• Status: Not yet recruiting
• Conditions: Cardiac Surgery; Acute Postoperative Pain; Chronic Post-surgical Pain
• Intervention / Treatment: Procedure: Standard Multimodal Opioid-Based Analgesia; Procedure: Regional Anesthesia-Based Analgesia

Detailed Description

Chronic post-surgical pain (CPSP) is a common and clinically significant complication following cardiac surgery and is associated with impaired functional recovery, reduced quality of life, prolonged opioid exposure, and increased healthcare utilization. Despite substantial advances in perioperative care, a considerable proportion of patients continue to experience persistent pain for months after surgery. The pathophysiology of CPSP is multifactorial and involves complex interactions among surgical tissue injury, peripheral and central sensitization, neuroinflammatory activation, altered pain modulation pathways, and psychosocial vulnerability factors.

Optimization of perioperative analgesia has been proposed as a strategy to reduce nociceptive input, attenuate perioperative stress responses, and potentially decrease the risk of pain chronification. Regional anesthesia techniques, particularly chest wall plane blocks, have demonstrated beneficial effects on acute postoperative pain control and opioid-sparing outcomes in cardiac surgery. However, their influence on long-term pain outcomes and the development of CPSP remains incompletely understood.

The CROPS study (Chronification of Post-Surgical Pain and Risk Assessment) is a prospective multicenter randomized controlled trial designed to evaluate the impact of perioperative analgesic strategies on postoperative recovery and chronic pain development in adult patients undergoing cardiac surgery. Participants will be randomized to receive either standard multimodal opioid-based perioperative analgesia or regional anesthesia-based perioperative analgesia incorporating chest wall plane block techniques, including erector spinae plane block, paravertebral block, or PECS block, according to institutional practice.

The study will compare postoperative pain intensity, opioid consumption, postoperative recovery parameters, postoperative complications, health-related quality of life, and the incidence of chronic post-surgical pain at 3 months after surgery. Particular emphasis will be placed on evaluating whether regional anesthesia-based analgesic strategies reduce perioperative opioid exposure and improve both short-term and long-term patient-centered outcomes.

In parallel, the study aims to validate a novel questionnaire-based pain chronification risk assessment tool intended to identify patients at increased risk of developing CPSP. Predictive performance of the questionnaire will be evaluated using receiver operating characteristic (ROC) analysis, including assessment of area under the curve (AUC), sensitivity, specificity, discrimination, and calibration performance.

The primary outcome measures are the incidence of chronic post-surgical pain at 3 months following surgery and the predictive accuracy of the pain chronification risk assessment questionnaire. Secondary outcomes include postoperative pain intensity, perioperative opioid consumption expressed as morphine milligram equivalents, postoperative nausea and vomiting, postoperative recovery parameters, respiratory complications, duration of mechanical ventilation, intensive care unit length of stay, hospital length of stay, postoperative complications, in-hospital mortality, and changes in quality-of-life and pain-related functional outcome measures.

The study is conducted as an investigator-initiated multicenter academic collaboration between the East Slovakia Institute of Cardiovascular Diseases, Košice, Slovakia, and Uppsala University Hospital, Uppsala, Sweden.

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ladislav Kočan, assoc. prof, MD, PhD; Phone Number: +421557891110; Email: lkocan@vusch.sk
• Study Contact Backup: Name: Peter Kostič, MD PhD; Email: peter.kostic@uu.se

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥18 years
• Elective cardiac surgery requiring median sternotomy, including:
• coronary artery bypass grafting (CABG)
• aortic valve replacement or repair
• mitral valve replacement or repair
• ascending aorta surgery
• Ability to understand study information
• Ability to provide written informed consent
• Expected postoperative hospital stay longer than 3 days
• Availability for follow-up at 1 week and 3 months after surgery

Exclusion Criteria:

• Emergency surgery
• Cognitive impairment preventing study participation
• Serious psychiatric illness interfering with study participation
• Language barrier preventing questionnaire completion
• Participation in another interventional study affecting pain outcomes
• Reoperation for postoperative bleeding
• Severe chronic renal failure
• Allergy or contraindication to study medication or regional anesthesia techniques
• Pregnancy or breastfeeding
• Chronic opioid therapy exceeding 60 mg morphine equivalents daily
• Extensive emergency aortic surgery (e.g., Thoraflex implantation for acute aortic dissection)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard Multimodal Opioid-Based Analgesia; Participants will receive standard multimodal opioid-based perioperative analgesia according to institutional cardiac surgery pain management protocols.	Procedure: Standard Multimodal Opioid-Based Analgesia; Standard perioperative pain management including opioid-based multimodal analgesia administered according to institutional cardiac surgery protocols.
Experimental: Regional Anesthesia-Based Analgesia; Participants will receive regional anesthesia-based perioperative analgesia including chest wall plane block techniques in combination with multimodal analgesia during cardiac surgery.	Procedure: Regional Anesthesia-Based Analgesia; Regional anesthesia-based perioperative analgesia including chest wall plane block techniques such as erector spinae plane block, PECS block, or paravertebral block in combination with multimodal analgesia during cardiac surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Chronic Post-Surgical Pain at 3 Months	Presence of chronic post-surgical pain assessed 3 months after surgery using the Brief Pain Inventory questionnaire and pain intensity evaluation.	3 months after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative Pain Intensity	Postoperative pain intensity assessed using the Visual Analogue Scale (VAS) ranging from 0 (no pain) to 10 (worst imaginable pain), assessed four times daily during the first postoperative week.	Postoperative days 1-7
Perioperative Opioid Consumption	Total perioperative and postoperative opioid consumption expressed as morphine milligram equivalents (MME).	Postoperative days 1-7
Brief Pain Inventory Score Changes	Changes in Brief Pain Inventory (BPI) questionnaire scores ranging from 0 to 10, where higher scores indicate worse pain severity and pain interference, assessed between baseline, postoperative week 1, and 3-month follow-up.	Baseline, 1 week, and 3 months after surgery
Validation of Pain Chronification Risk Assessment Questionnaire	Predictive performance of the questionnaire for chronic post-surgical pain development assessed using ROC analysis, sensitivity, and specificity.	Baseline assessment with 3-month follow-up
Quality of Life Assessment	Quality of life evaluated using the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) and EQ Visual Analogue Scale (EQ-VAS), where higher scores indicate better health status.	Baseline and 3 months after surgery
Perioperative Vasopressor Requirement	Requirement for perioperative vasopressor support assessed by norepinephrine administration duration and cumulative dose during surgery and intensive care unit stay.	From surgery until postoperative day 7
Cardiopulmonary Bypass and Surgical Parameters	Operative and cardiopulmonary bypass parameters including duration of surgery, cardiopulmonary bypass time, and aortic cross-clamp time.	Intraoperative period
Duration of Mechanical Ventilation	Duration of postoperative mechanical ventilation measured in hours from ICU admission until successful extubation.	Postoperative period through day 7
Intensive Care Unit Length of Stay	Length of stay in the intensive care unit measured in days.	Up to 30 days after surgery
Hospital Length of Stay	Total postoperative hospital length of stay measured in days.	Up to 30 days after surgery
Postoperative Complications	Number of participants experiencing postoperative complications including respiratory, cardiovascular, neurological, infectious, or surgical complications.	Up to 30 days after surgery
In-Hospital Mortality	Number of participants who die during the index hospitalization.	Up to 30 days after surgery

Collaborators and Investigators

• Sponsor: Kočan Ladislav
• Collaborators: Uppsala University Hospital; East Slovakia Institute of Cardiovascular Diseases in Košice, Slovakia
• Investigators: Study Chair: Peter Kostic, MD, PhD, Department of Heart and Lung Diseases, Unit for Cardiothoracic Surgery, Anesthesia and Intensive Care, Uppsala University Hospital, 751 85 Uppsala, Sweden

Publications and helpful links

General Publications

• Martuliak I, Golubnitschaja O, Chvala L, Kapalla M, Ferencik M, Bubeliny M, Venglarcik M, Kocan L. Pain chronification risk assessment: advanced phenotyping and scoring for prediction and treatments tailored to individualized patient profile. EPMA J. 2024 Nov 15;15(4):739-750. doi: 10.1007/s13167-024-00383-3. eCollection 2024 Dec.

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: May 17, 2026
• First Submitted That Met QC Criteria: June 4, 2026
• First Posted (Actual): June 5, 2026

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: cardiac surgery; chronic post-surgical pain; postoperative analgesia; regional anesthesia
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain, Postoperative
• Other Study ID Numbers: CROPS-INT-RCT-2026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data sharing has not yet been determined. Data sharing policies will be evaluated after study completion in accordance with institutional regulations, ethical approvals, and patient privacy requirements.

Drug and device information, study documents

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