Stimulation pupillometry as a predictor of the nociceptive response and a tool for comparing regional blockades during thoracoscopic operations (randomized trial)

Introduction. For effective pain relief in thoracic surgery, accurate monitoring of analgesia is essential. A promising method is pupillometry, which assesses the pupil’s response to pain faster and more accurately than traditional indicators (blood pressure, heart rate). The combination of pupillometry with electrocutaneous stimulation will make it possible to objectively assess the depth of analgesia and optimize anesthesia support in video-assisted thoracoscopic surgeries.

The objective was to assess whether stimulation pupillometry predicts the severity of the intraoperative nociceptive response and allows an objective comparison of the analgesic effectiveness of regional blockades in thoracoscopic operations.

Materials and methods. A blinded, placebo-controlled, prospective, single-center, randomized (envelope method) study to analyze the efficacy of combined anesthesia based on paravertebral block, serratus anterior plane block, intraoperative erector spinae plane block by electrocutaneous stimulation and pupillometry included 120 patients who underwent elective thoracoscopic surgery. All study participants were divided into 4 groups: 1 – combined general anesthesia – control group (CGA); 2 – combined anesthesia with paravertebral block (PVB); 3 – combined anesthesia with serratus anterior plane block (SAP block); 4 – combined anesthesia with erector spinae plane block (ESP- block). Electrocutaneous irritation and pupillometry were used to assess the analgesic effect of regional blockades at 4 stages of the perioperative period.

Results. Analysis of pain sensitivity thresholds did not reveal significant differences between the groups (p = 0.861), the median values were 7.0–8.0 mA. Nociceptive response by pupillometry revealed a statistically significant increase in pupil diameter in response to electrical stimulation and surgical incision in all groups (p ≤ 0.001), with the maximum increase in the CGA group compared to regional blockades (PVB, ESP, SAP). Hemodynamic parameters (mean BP, HR) showed unidirectional dynamics with a moderate increase in nociceptive stimulation. The largest increase in mean BP was noted in the CGA, the minimum – in the ESP block (p < 0.005). A similar pattern was observed for heart rate with a more pronounced response in the CGA and ESP block groups. An analysis of the need for opioid analgesics showed equivalent doses of fentanyl in all groups, but glucose levels were significantly higher with CGA and SAP block (p < 0.05), indicating a more pronounced stress response.

Conclusion. Regional methods of anesthesia provide more effective suppression of the nociceptive response compared to combined general anesthesia. The body’s response to electrodermal irritation can be used as a predictor of the intensity of the pain response.

1. Aleksandrovich L. P. Influence of regional anesthesia on metabolic and inflammatory changes in abdominal operations. General Reanimatology, 2011, no 2, pp. 31–34. (In Russ.). https://doi.org/10.15360/1813-9779-2011-2-31

2. BazarovD. V.,ToneevM. A.,VyzhiginaM. A. et al. Multidisciplinaryapproachto postoperativetherapy.Russian magazine of pain, 2019, no 2, pp.14–19.(In Russ.). http://doi.org/10.25731/RASP.2019.02.15.

3. Ivanishcheva Yu. A., Zaitsev A. Yu., Kavochkin A. A. et al. The effect of atropine on the accuracy of pupillometry as a method of diagnosing the analgesic component of general anaesthesia. Messenger of anesthesiology and resuscitation, 2025, vol. 22, no. 5, pp. 15–20. (In Russ.). https://doi.org/10.24884/2078-5658-2025-22-5-15-20.

4. Tarasova N. Yu., Shmigelevsky A. V., Lubnin A. Yu., Kulikov A. S. Quantitative intraoperative monitoring of analgesia. Anesthesiology and resuscitation, 2020, no. 3, pp. 27–36. (In Russ.). http://doi.org/10.17116/anaesthesiology202003127

5. Tsvetkov D. S., Chernysheva E. D., Shin A. R. Paravertebral blockade in thoracic anesthesiology. Russian magazine of pain, 2013, no 3, pp. 3–7. (In Russ.).

6. Achamallah N., Fried J., Sharma R. et al. Pupillary light reflex is not abolished by epinephrine and atropine given during advanced cardiac life support in patients who achieve return of spontaneous circulation. Journal of intensive care medicine, 2020, vol. 36, no. 4, pp. 459–465. http://doi.org/10.1177/0885066620906802.

7. Baidya D. K., Khanna P., Maitra S. Analgesic efficacy and safety of thoracic paravertebral and epidural analgesia for thoracic surgery: a systematic review and meta-analysis. Interact Cardiovasc Thorac Surg, 2014, vol. 18, no. 5, pp. 626–635. http://doi.org/10.1093/icvts/ivt551.

8. Barvais L.,Engelman E.,Eba J. M.et al. Effect site concentrations of remifentanil and pupil response to noxious stimulation.Br J Anaesth, 2003,vol. 91,no. 13,pp.347–352. http://doi.org/10.1093/bja/aeg178.

9. Brodsky J. B., Cohen E. Video-assisted thoracoscopic surgery. Current Opinion in Anesthesiology, 2000, vol. 13, no. 1, pp. 41. http://doi.org/10.1097/00001503-200002000-00007.

10. Davies R. G., Myles P. S., Graham J. M. A comparison of the analgesic efficacy and side-effects of paravertebral vs epidural blockade for thoracotomy. Br J Anaesth, 2006, vol. 96, no. 4, pp. 418–426. http://doi.org/10.1093/bja/ael020.

11. Finnerty D. T., McMahon A., McNamaraet J. R. al. Comparing erector spinae plane block with serratus anterior plane block for minimally invasive thoracic surgery. Br J Anaesth, 2020, vol. 125, no. 5, pp. 802–810. http://doi.org/10.1016/j.bja.2020.06.020.

12. Gaballah K. M., Soltan W. A, Bahgat N. M.https://pubmed.ncbi.nlm.nih.gov/30930141/ - full-view-affiliation-1 Ultrasound-guided serratus plane block versus erector spinae block for postoperative analgesia after VATS. J Cardiothorac Vasc Anesth, 2019, vol. 33, no. 7, pp. 1946–1953. http://doi.org/10.1053/j.jvca.2019.02.028.

13. Kaplowitz J., Papadakos P. J. Acute pain management for video-assisted thoracoscopic surgery: an update. Journal of Cardiothoracic and Vascular Anesthesia, 2012, vol. 26, no. 2, pp. 312–321. http://doi.org/10.1053/j.jvca.2011.04.010.

14. Kornilov E., Gehlen L., Yacobi D. et al. Pupillary pain index predicts postoperative pain but not the effect of peripheral regional anaesthesia in patients undergoing total hip or total knee arthroplasty: an observational study. Medicina (Kaunas), 2023, vol. 59, no. 5, pp. 826. http://doi.org/10.1097/EJA.0b013e32835f0030.

15. Larson M. D. Mechanism of opioid-induced pupillary effects. Clin Neurophysiol, 2008, vol. 119, no. 6, pp. 1358–1364. http://doi.org/10.1016/j.clinph.2008.01.106.

16. Larson M. D., Behrends M. Portable infrared pupillometry: a review. Anesthesia & Analgesia, 2015, vol. 120, no. 6, pp. 1242–1253. http://doi.org/10.1213/ANE.0000000000000314.

17. Larson M. D., Talke P. O. Effect of dexmedetomidine, an alpha2 – adrenoceptor agonist, on human pupillary reflexes during general anaesthesia. Br J Clin Pharmacol, 2001, vol. 51, no. 1, pp. 27–33. http://doi.org/10.1046/j.1365-2125.2001.01311.x.

18. Taketa Y., Irisawa Y., Fujitani T. Comparison of ultrasound-guided erector spinae plane block and thoracic paravertebral block for postoperative analgesia after VATS. Reg Anesth Pain Med, 2020, vol. 45, pp. 10–15. http://doi.org/10.1136/rapm-2019-100827.