THE ROLE OF PAIN AS A RESPIRATORY STIMULANT: A CASE REPORT OF SUDDEN RESPIRATORY DEPRESSION FOLLOWING REGIONAL ANESTHESIA IN A PATIENT ON HIGH-DOSE OXYCODONE

Izabella Kula; Emilia Kucab; Anna Kołodziej; Kacper  Szpanelewski; Radosław Kołodziej; Szymon Lulek; Jakub Klecha; Szczepan Półchłopek; Katarzyna Dziki; Joanna  Ciemięga; Wiktor Adamiec; Damian Danilczuk

doi:10.31435/ijitss.3(51).2026.5754

Authors

Izabella Kula City Hospital of John Paul II in Rzeszów, Rzeszów, Poland https://orcid.org/0009-0002-7379-5062
Emilia Kucab University Clinical Hospital F.Chopin in Rzeszów, Rzeszów, Poland https://orcid.org/0000-0003-4320-6327
Anna Kołodziej Saint Queen Jadwiga Clinical Regional Hospital in Rzeszów, Rzeszów, Poland https://orcid.org/0009-0001-0969-5211
Kacper Szpanelewski Saint Queen Jadwiga Clinical Regional Hospital in Rzeszów, Rzeszów, Poland https://orcid.org/0009-0006-2517-4535
Radosław Kołodziej Saint Queen Jadwiga Clinical Regional Hospital in Rzeszów, Rzeszów, Poland https://orcid.org/0009-0009-1767-5956
Szymon Lulek Saint Queen Jadwiga Clinical Regional Hospital in Rzeszów, Rzeszów, Poland https://orcid.org/0009-0000-3827-2907
Jakub Klecha Saint Queen Jadwiga Clinical Regional Hospital in Rzeszów, Rzeszów, Poland https://orcid.org/0009-0003-8909-9181
Szczepan Półchłopek City Hospital of John Paul II in Rzeszów, Rzeszów, Poland https://orcid.org/0000-0003-1188-2830
Katarzyna Dziki University Clinical Hospital F.Chopin in Rzeszów, Rzeszów, Poland https://orcid.org/0009-0003-9380-1244
Joanna Ciemięga University of Rzeszów: Rzeszów, Rzeszów Poland https://orcid.org/0009-0009-0041-1671
Wiktor Adamiec City Hospital of John Paul II in Rzeszów, Rzeszów, Poland https://orcid.org/0009-0002-3322-5479
Damian Danilczuk City Hospital of John Paul II in Rzeszów, Rzeszów, Poland https://orcid.org/0009-0005-5755-1115

DOI:

https://doi.org/10.31435/ijitss.3(51).2026.5754

Keywords:

Oxycodone, Bupivacaine, Respiratory Depression, Cancer Pain, Opioid-Induced Hyperalgesia (OIH), Regional Anesthesia

Abstract

This study provides a detailed case report of a 65-year-old patient with disseminated cancer who was receiving extremely high doses of oxycodone (2 g/day) for severe, uncontrolled pain. A suprascapular nerve block with bupivacaine provided almost immediate relief; however, after 25 minutes, it led to sudden respiratory arrest. This event necessitated urgent emergency medical intervention and ICU hospitalization. Clinical analysis ruled out local anesthetic systemic toxicity (LAST), identifying the physiological antagonism between nociception and the respiratory depressive effects of opioids as the cause. Pain, acting as a natural respiratory stimulant, masked the effects of severe oxycodone overdose. The block's analgesic effect abruptly removed this stimulus, resulting in apnea. The article discusses the underlying mechanisms and provides a differential diagnosis between tolerance and opioid-induced hyperalgesia (OIH). It emphasizes the importance of multimodal treatment, including ultra-low-dose naloxone, to prevent dose escalation. The findings indicate a critical need for hospitalizing patients requiring high analgesic doses for safe titration and the necessity of intensive monitoring during regional anesthesia in opioid-dependent individuals.

Introduction: The aim of this paper is to present and analyze a rare but life-threatening complication: respiratory arrest following local anesthesia in an oncology patient receiving extremely high doses of opioids. The work highlights the physiological role of pain as an antagonist of opioid-induced respiratory depression.

Methodology: A case of a 65-year-old male with disseminated cancer, treated with an extremely high dose of oxycodone (2 g/day), is described. Due to severe shoulder pain, a suprascapular nerve block was performed using 5 ml of 0.5% bupivacaine and methylprednisolone. A literature review was conducted to differentiate the causes of apnea, including the exclusion of Local Anesthetic Systemic Toxicity (LAST).

Results: Pain subsided almost immediately following the procedure; however, after 25 minutes, the patient experienced sudden apnea requiring intubation and ICU hospitalization. Analysis excluded technical error and systemic toxicity (LAST) based on dosage and symptom dynamics. The most likely cause was the elimination of the painful stimulus, which previously stimulated the respiratory center and balanced the depressive effects of high-dose oxycodone.

References

Wordliczek, J., Kotlińska-Lemieszek, A., Leppert, W., Woroń, J., Dobrogowski, J., Krajnik, M., Przeklasa-Muszyńska, A., Jassem, J., & Drobnik, J. (2018). Pharmacotherapy of pain in cancer patients: Recommendations of the Polish Association for the Study of Pain. Polish Journal of Surgery.

Owczuk, R. (2023). Anesthesiology and intensive therapy (pp. 151–152, 313). PZWL.

Dzierżanowski, T., & Ciałkowska-Rysz, A. (2010). Oxycodone: First-line drug in the treatment of severe cancer pain. Medycyna Paliatywna/Palliative Medicine, 2(3), 123–131.

Polish Society of Mountain Medicine and Rescue. (2019). Position on the treatment of frostbite. http://176.114.232.105/public/ckfinder/userfiles/files/NAJNOWSZA%20WERSJA%20KONSENSUSU%20DO%20DRUKU%2010%202019.pdf

Summary of product characteristics: OxyContin. (n.d.). Rejestry Medyczne. https://rejestrymedyczne.ezdrowie.gov.pl/api/rpl/medicinal-products/19285/characteristic

Pergolizzi, J., Böger, R. H., Budd, K., Dahan, A., Erdine, S., Hans, G., Kress, H. G., Langford, R., Likar, R., Raffa, R. B., et al. (2009). Opioids and management of severe chronic pain in the elderly: Consensus of an international expert panel. Palliative Medicine.

Therapeutic Goods Administration. (n.d.). Product information: OxyContin. https://www.tga.gov.au/sites/default/files/foi-1299-74.pdf

Shafiei, F. T., McAllister, R. K., & Lopez, J. (2024). Bupivacaine. In StatPearls. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK532883/

Gola, W., Domagała, M., Cugowski, A., Zając, M., & Czuczwar, M. (2018). Local anesthetic systemic toxicity (LAST): Current state of knowledge. Anestezjologia i Ratownictwo, 12, 327–333.

Nozaki-Taguchi, N., Ueda, Y., Inada, A., Son, K., & Isono, S. (2020). A report of three cancer patients on opioid analgesia receiving spinal anesthesia: Abrupt pain elimination without respiratory depression. JA Clinical Reports, 6(1), Article 49. https://doi.org/10.1186/s40981-020-00355-2

Hohwü, L., Akre, O., Bergenwald, L., Törnblom, M., & Gustafsson, O. (2006). Oral oxycodone hydrochloride versus epidural anaesthesia for pain control after radical retropubic prostatectomy. Scandinavian Journal of Urology and Nephrology, 40(3), 192–197.

Lamplot, J. D., Wagner, E. R., & Manning, D. W. (2014). Multimodal pain management in total knee arthroplasty: A prospective randomized controlled trial. The Journal of Arthroplasty, 29(2), 329–334. https://doi.org/10.1016/j.arth.2013.06.005

Borgbjerg, M. F., Nielsen, K., & Franks, J. (1996). Experimental pain stimulates respiration and attenuates morphine-induced respiratory depression: A controlled study in human volunteers. Pain, 64(1), 123–128. https://doi.org/10.1016/0304-3959(95)00088-7

Moores, M. A. (1988). Single breath induction of anaesthesia with isoflurane. British Journal of Anaesthesia, 61(1), 121–122. https://doi.org/10.1093/bja/61.1.121

Pattinson, K. T. S. (2008). Opioids and the control of respiration. British Journal of Anaesthesia, 100(6), 747–758. https://doi.org/10.1093/bja/aen093

Piquet, C. Y., Mallaret, M. P., Lemoigne, A. H., Barjhoux, C. E., Danel, V. C., & Vincent, F. H. (1998). Respiratory depression following administration of intrathecal bupivacaine to an opioid-dependent patient. The Annals of Pharmacotherapy, 32(6), 653–655. https://doi.org/10.1345/aph.17182

Kotlińska-Lemieszek, A., Klepstad, P., & Haugen, D. F. (2015). Clinically significant drug–drug interactions involving opioid analgesics used for pain treatment in patients with cancer: A systematic review. Drug Design, Development and Therapy, 9, 5255–5267. https://doi.org/10.2147/DDDT.S86983

Zylicz, Z., Twycross, R., & Krajnik, M. (2010). Opioid antagonists may be useful in control of intractable pain in advanced disease: A case series. Advances in Palliative Medicine, 9(4), 123–128.

Bateman, J. T., Saunders, S. E., & Levitt, E. S. (2023). Understanding and countering opioid-induced respiratory depression. British Journal of Pharmacology, 180(7), 813–828. https://doi.org/10.1111/bph.15580

D’Souza, M. S., Pham, H., & Ray, S. D. (2022). Side effects of opioid analgesics and narcotic antagonists. In S. D. Ray (Ed.), Side effects of drugs annual (Vol. 44, pp. 173–184). Elsevier. https://doi.org/10.1016/bs.seda.2022.09.002

Wilson, S. H., Hellman, K. M., James, D., Adler, A. C., & Chandrakantan, A. (2021). Mechanisms, diagnosis, prevention and management of perioperative opioid-induced hyperalgesia. Pain Management, 11(4), 405–417. https://doi.org/10.2217/pmt-2020-0105

Umukoro, N. N., Aruldhas, B. W., Rossos, R., Pawale, D., Renschler, J. S., & Sadhasivam, S. (2021). Pharmacogenomics of oxycodone: A narrative literature review. Pharmacogenomics, 22(5). https://doi.org/10.2217/pgs-2020-0144

Woods, G. W., O’Connor, D. P., & Calder, C. T. (2006). Continuous femoral nerve block versus intra-articular injection for pain control after anterior cruciate ligament reconstruction. The American Journal of Sports Medicine, 34(8), 1328–1333. https://doi.org/10.1177/0363546506286740

Dahan, A. (2006). Opioid-induced respiratory effects: New data on buprenorphine. Expert Opinion on Drug Safety. https://pubmed.ncbi.nlm.nih.gov/16764215/