Background & Aims

Acute postoperative pain is a major contributor to complications and prolonged admission time after Video-Assisted Thoracoscopic Surgery (VATS)1. A variety of perioperative factors have been proposed as predictors of acute postoperative pain, e.g., psychological factors2, pain sensitivity3, demographics, and surgical characteristics4. Inflammation might be crucial, as pro-inflammatory cytokines can lead to a sensitization of peripheral and central pain mechanisms and sensitization of these pathways is associated to chronic postoperative pain5. Preoperative expression of pro-inflammatory blood biomarkers has been associated with chronic pain following total knee arthroplasty surgey6, but this have not been studied in VATS. Therefore, this exploratory study aimed to examine if preoperative inflammatory markers are associated with acute postoperative pain and opioid consumption after VATS.

Methods

Patients scheduled to undergo VATS due to presumed or confirmed lung cancer were included. Blood samples were drawn prior to surgery and stored at -80°C until analysis. Plasma samples were analyzed with the OLINK target 92 inflammatory assay, which gives plasma levels of 92 established or experimental inflammatory markers. Postoperative pain was estimated based on cumulative opioid consumption within the first 48 hours after surgery. Pain was reported twice daily using a Numerical Rating Scale (NRS) and the area under the curve (NRSAUC) for the first 48 hours after surgery was utilized. In this preliminary analysis, two groupings were defined, as a median split of consumption of opioids. Additionally, patients with an average score above 2 of NRSAUC were classified as high pain responders. The groups were compared using students t-tests. A p-value of 0.05 was considered significant.

Results

Between October 2022 and August 2023, a total of 100 patients were included with a median age of 70.7 [IQR 47.6 – 84.3] and 49% males. Of the 100 samples, 93 passed quality control and were included in this analysis. There were 47 patients in the high opioid group and 46 in the low opioid group. There were 58 classified as low pain responders and 35 as high pain responders. Of the 92 inflammatory markers, 41 had sufficient levels to be analyzed. The level of biomarker CXCL9 was significantly higher (7.6 pg/ml versus 8.1 pg/ml, p = 0.015) in patients with a high compared to low opioid consumption. No differences in any of the analyzed proteins levels were found between low pain responders and high pain responders.

Conclusions

In this preliminary exploratory analysis, 41 proteins were analyzed and preoperative CXCL9 levels were found to be elevated in patients with high compared to low opioid consumption after VATS. This finding should be confirmed in large scale studies before definitive conclusion should be made.

References

1. Huang L, Kehlet H, Petersen RH: Reasons for staying in hospital after video-assisted thoracoscopic surgery lobectomy. BJS Open 2022; 6
2. Bayman EO, Parekh KR, Keech J, Larson N, Weg M Vander, Brennan TJ: Preoperative patient expectations of postoperative pain are associated with moderate to severe acute pain after VATS. Pain Medicine (United States) 2019; 20:543–54
3. Weissman-Fogel I, Granovsky Y, Crispel Y, Ben-Nun A, Best LA, Yarnitsky D, Granot M: Enhanced Presurgical Pain Temporal Summation Response Predicts Post-Thoracotomy Pain Intensity During the Acute Postoperative Phase. Journal of Pain 2009; 10:628–36
4. Schnabel A, Yahiaoui-Doktor M, Meissner W, Zahn PK, Pogatzki-Zahn EM: Predicting poor postoperative acute pain outcome in adults: An international, multicentre database analysis of risk factors in 50,005 patients. Pain Rep 2020; 5:1–8
5. Ji RR, Nackley A, Huh Y, Terrando N, Maixner W: Neuroinflammation and central sensitization in chronic and widespread pain. Anesthesiology 2018; 129:343–66
6. Giordano R, Ghafouri B, Arendt-Nielsen L, Petersen KK-S: Inflammatory biomarkers in patients with painful knee osteoarthritis: exploring the potential link to chronic postoperative pain after total knee arthroplasty—a secondary analysis. Pain 2023 doi:10.1097/j.pain.0000000000003042

Presenting Author

Phillip K Sperling

Poster Authors

Phillip Sperling

MD

Aalborg University and Aalborg University Hospital

Lead Author

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Allan Vestergaard Danielsen

Department of Cardiothoracic Surgery, Aalborg University Hospital, Aalborg, Denmark

Lead Author

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Bodil Steen Rasmussen

Department of Anaesthesiology and Intensive Care, Aalborg University Hospital, Aalborg, Denmark

Lead Author

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Kristian Petersen

PhD

Aalborg University, Aalborg, Denmark

Lead Author

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Jannie Bisgaard

Department of Anaesthesiology and Intensive Care, Aalborg University Hospital, Aalborg, Denmark

Lead Author

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Rocco Giordano

Center for Neuroplasticity and Pain, HST, Faculty of Medicine, Aalborg University, Aalborg, DK

Lead Author

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