Short-term perfusion and respiratory effects of dexketoprofen, tramadol, and their combination in renal colic: A prospective randomized capnography study
Abstract
Objective: Intravenous non-steroidal anti-inflammatory drugs (NSAIDs) and opioids, including dexketoprofen trometamol and tramadol, remain the primary analgesic options for treating acute renal colic in emergency departments. However, concerns about respiratory depression associated with opioids can limit the use of tramadol with confidence, and there are limited data on the short-term respiratory and perfusion effects of these agents. The present study aimed to evaluate the short-term effects of intravenous dexketoprofen trometamol, tramadol, and their combination on tissue perfusion and respiratory function. The study assessed these effects using EtCO₂ and related physiological parameters. The study population comprised hemodynamically stable emergency department patients presenting with acute renal colic.
Methods: In this prospective, randomized, controlled trial conducted in an academic emergency department, adults aged 18–55 with acute renal colic received one of three intravenous regimens: dexketoprofen trometamol (50 mg), tramadol (100 mg), or their 50 mg/50 mg combination. Vital signs, SpO₂, and EtCO₂ were recorded at baseline, 30, and 60 minutes; arterial blood gases, including lactate, were drawn at baseline and 60 minutes. The primary endpoint of the study was the EtCO₂ trajectory over time.
Results: In a study of 102 patients (with 34 patients in each group), EtCO₂, heart rate, and blood pressure were found to be similar between the groups at all measured time points. Furthermore, analysis using mixed-effects models revealed no significant group-by-time interactions. SpO₂ levels were found to be lower in the combination group compared to the dexketoprofen group at the 60-minute mark (93.8% vs. 95.4%; ANOVA p = 0.018; post hoc p = 0.016). In the present study, seven patients, all in tramadol-containing arms, exhibited transient SpO₂ levels below 90%, though none of these patients required oxygen supplementation. The blood-gas parameters demonstrated stability, while lactate levels exhibited a significant decrease across all groups, without any observed between-group variation.
Conclusion: In patients with renal colic who were hemodynamically stable, the three treatment plans resulted in similar short-term effects on EtCO2, hemodynamics, and blood-gas parameters. The findings of this study demonstrate that modest SpO₂ declines, accompanied by transient desaturations in the tramadol-containing arms, provide substantiated support for the implementation of pulse oximetry and capnography monitoring when tramadol is administered. It should be noted that the study was not designed to assess comparative safety, and thus the findings should be considered physiological observations only. The lactate reduction may be indicative of a resolution of pain-related stress; however, this remains a hypothesis that requires further investigation.
Trial Registration: The study was registered at ClinicalTrials.gov (ID: NCT07386288). Registration was retrospective.Keywords
References
Patti L, Leslie SW. Acute renal colic. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan– [updated 2024 Dec 23; cited 2026 Oct 19]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK431091/
Golzari SE, Soleimanpour H, Rahmani F, Zamani Mehr N, Safari S, Heshmat Y, et al. Therapeutic approaches for renal colic in the emergency department: a review article. Anesth Pain Med. 2014;4(1):e16222. https://doi.org/10.5812/aapm.16222
Skolarikos A, Geraghty R, Somani B, Tailly T, Jung H, Neisius A, et al. European Association of Urology guidelines on the diagnosis and treatment of urolithiasis. Eur Urol. 2025;88(1):64-75. https://doi.org/10.1016/j.eururo.2025.03.011
Broder JS, Oliveira J E Silva L, Bellolio F, Freiermuth CE, Griffey RT, Hooker E, et al. Guidelines for Reasonable and Appropriate Care in the Emergency Department 2 (GRACE-2): low-risk, recurrent abdominal pain in the emergency department. Acad Emerg Med. 2022;29(5):526-60. https://doi.org/10.1111/acem.14495
Morgan S. Intravenous paracetamol in patients with renal colic. Emerg Nurse. 2011;18(9):22-5. https://doi.org/10.7748/en2011.02.18.9.22.c8337
Holdgate A, Pollock T. Nonsteroidal anti-inflammatory drugs (NSAIDs) versus opioids for acute renal colic. Cochrane Database Syst Rev. 2004;(1):CD004137. https://doi.org/10.1002/14651858.CD004137.pub2
Pathan SA, Mitra B, Cameron PA. A systematic review and meta-analysis comparing the efficacy of nonsteroidal anti-inflammatory drugs, opioids, and paracetamol in the treatment of acute renal colic. Eur Urol. 2018;73(4):583-95. https://doi.org/10.1016/j.eururo.2017.11.001
Cabo JJS, Miller NL. Nonopioid pain management pathways for stone disease. J Endourol. 2024;38(2):108-20. https://doi.org/10.1089/end.2023.0266
Özdemir M, Çığşar G, Bağcıoğlu M, Çiftçi H, Günal E. Comparison of the analgesic effects of intravenous dexketoprofen, ibuprofen and fentanyl in patients suffering from renal colic pain in the emergency department. Eurasian J Emerg Med. 2023;22(1):18-23. https://doi.org/10.4274/eajem.galenos.2022.20633
National Institute for Health and Care Excellence. Renal and ureteric stones: assessment and management [Internet]. London: NICE; 2019 [cited 2026 Oct 19]. NICE guideline NG118. Available from: https://www.nice.org.uk/guidance/ng118
Gu HY, Luo J, Wu JY, Yao QS, Niu YM, Zhang C. Increasing nonsteroidal anti-inflammatory drugs and reducing opioids or paracetamol in the management of acute renal colic: based on three-stage study design of network meta-analysis of randomized controlled trials. Front Pharmacol. 2019;10:96. https://doi.org/10.3389/fphar.2019.00096
Subedi M, Bajaj S, Kumar MS, Yc M. An overview of tramadol and its usage in pain management and future perspective. Biomed Pharmacother. 2019;111:443-51. https://doi.org/10.1016/j.biopha.2018.12.085
Aminiahidashti H, Shafiee S, Zamani Kiasari A, Sazgar M. Applications of end-tidal carbon dioxide (ETCO₂) monitoring in emergency department; a narrative review. Emerg (Tehran). 2018;6(1):e5. https://pubmed.ncbi.nlm.nih.gov/29503830/
Kheng CP, Rahman NH. The use of end-tidal carbon dioxide monitoring in patients with hypotension in the emergency department. Int J Emerg Med. 2012;5(1):31. https://doi.org/10.1186/1865-1380-5-31
Zhang Y, Zhou R. A review of using CO₂-derived variables to detect tissue hypoperfusion during cardiopulmonary bypass. Perfusion. 2024;39(3):445-51. https://doi.org/10.1177/02676591221151028
Burton JH, Harrah JD, Germann CA, Dillon DC. Does end-tidal carbon dioxide monitoring detect respiratory events prior to current sedation monitoring practices? Acad Emerg Med. 2006;13(5):500-4. https://doi.org/10.1197/j.aem.2005.12.017
Miner JR, Heegaard W, Plummer D. End-tidal carbon dioxide monitoring during procedural sedation. Acad Emerg Med. 2002;9(4):275-80. https://doi.org/10.1111/j.1553-2712.2002.tb01318.x
Tarkkila P, Tuominen M, Lindgren L. Comparison of respiratory effects of tramadol and oxycodone. J Clin Anesth. 1997;9(7):582-5. https://doi.org/10.1016/s0952-8180(97)00147-5
Narwade G, Chakrabarti S, Kaushik R, Kumar R, Gupta N, Gupta N, et al. Evaluation of end-tidal carbon dioxide as a marker of fluid responsiveness in mechanically ventilated patients with shock: a prospective study in a tertiary care center in India. Monaldi Arch Chest Dis. 2025 [published online 2025 Oct 14]. https://doi.org/10.4081/monaldi.2025.3387
Wang J, Weng L, Xu J, Du B. Mean 24-hour end-tidal carbon dioxide following diagnosis predicts mortality in patients with sepsis. World J Emerg Med. 2025;16(4):383-6. https://doi.org/10.5847/wjem.j.1920-8642.2025.067
Dogan B, Kudu E, Danış F, Ozturk Ince E, Karaca MA, Erbil B. Comparative analysis of perfusion index and end-tidal carbon dioxide in cardiac arrest patients: implications for hemodynamic monitoring and resuscitation outcomes. Cureus. 2023;15(12):e50818. https://doi.org/10.7759/cureus.50818
Hong KS, Lee JG, Kim TY, Lee JM, Park H, Lee H, et al. Utility of arterial to end-tidal carbon dioxide gradient as a severity index in critical care. Am J Med Sci. 2025;369(3):326-33. https://doi.org/10.1016/j.amjms.2024.10.007
Yaddanapudi LN, Wig J, Singh B, Tewari MK. Comparison of efficacy and side effects of epidural tramadol and morphine in patients undergoing laminectomy: a repeated dose study. Neurol India. 2000;48(4):398-400. https://pubmed.ncbi.nlm.nih.gov/11146613/
Park S, Lee GH, Kim S, Kim S, Kim Y, Choi SA. Risk factors for respiratory depression associated with tramadol based on the Global Pharmacovigilance Database (VigiBase). Pharmaceuticals (Basel). 2024;17(2):205. https://doi.org/10.3390/ph17020205
Houmes RJ, Voets MA, Verkaaik A, Erdmann W, Lachmann B. Efficacy and safety of tramadol versus morphine for moderate and severe postoperative pain with special regard to respiratory depression. Anesth Analg. 1992;74(4):510-4. https://doi.org/10.1213/00000539-199204000-00007
