Influence of intraoperative remifentanil and sufentanil on sensory perception: a randomized trial

Abstract

Objective: The clinical relevance of pro- and hyperalgesic effects of opioids is still a matter of debate. Particularly for remifentanil, an increased postoperative need for analgesics has been demonstrated suggesting opioid-induced hyperalgesia as a possible cause. The aim of the study was therefore to investigate the effect of intraoperatively applied remifentanil compared to sufentanil on somatosensory thresholds investigated with the quantitative sensory testing (QST) battery of the German Research Network on Neuropathic Pain (DFNS).

Research design and methods: Twenty-three patients undergoing surgery of the female breast were randomly assigned to intraoperative remifentanil (0.4 μg × kg⁻¹ × min⁻¹) or sufentanil (0.25 μg × kg⁻¹ bolus, 0.15 μg × kg⁻¹, repetition after 60 min) application. Anesthesia was maintained BIS-guided (Bispectral index^TM) with propofol and postoperative analgesia was ensured with paracetamol (max. 3 g/24 h). Quantitative sensory testing was performed in the region of dermatome Th 5 in the mid-axillary line preoperatively and 20 h postoperatively.

Clinical Trial registration: The study was registered at the German registry for clinical studies (DRKS00009002).

Main outcome measures: Comparison of somatosensory thresholds before versus after surgery and application of intraoperative remifentanil or sufentanil.

Results: Sixteen patients could be finally included in the analysis. No differences of mechanical or thermal detection or pain thresholds were observed between pre- and postoperative testing or between remifentanil and sufentanil.

Conclusion: A change of somatosensory thresholds or a clinically relevant opioid-induced hyperalgesia in the selected small patient sample (segmental resections or mastectomy with or without sentinel lymph node biopsy, surgery length <90 minutes, sufficient postoperative pain medication with paracetamol due to rather low postoperative pain intensities) with remifentanil or sufentanil was not detected 20 h after surgery.

Keywords:

• Opioid-induced hyperalgesia
• Postoperative pain
• Quantitative sensory testing
• Remifentanil
• Sufentanil

Transparency

Declaration of funding

The study was funded by the Dept. of Anaesthesiology and Intensive Care Medicine and the Division of Neurological Pain Research and Therapy, Department of Neurology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.

Author contributions: All authors contributed to study design, preparation of the manuscript and approved the final version of the manuscript. H.O., A.A. and J.G. also contributed to data collection and statistics.

Declaration of financial/other relationships

H.O. has disclosed that he has received speaking fees from Pfizer and CSL Behring. A.A. has disclosed that she has no significant relationships with or financial interests in any commercial companies related to this study or article. R.B. has received grants/research support from Pfizer, Genzyme GmbH, Grünenthal GmbH, Mundipharma. Furthermore, he is a member of the EU Project No 633491: DOLOR-isk and a member of the IMI “Europain” collaboration (industry members of the latter are: Astra Zeneca, Pfizer, Esteve, UCB-Pharma, Sanofi Aventis, Grünenthal GmbH, Eli Lilly and Boehringer Ingelheim Pharma GmbH&Co.KG). He has also received grants/research support from the German Federal Ministry of Education and Research (BMBF, ERA_NET NEU-RON/IM-PAIN Project), the German Research Network on Neuropathic Pain, NoPain system biology and the German Research Foundation (DFG). He has received speaking fees from Pfizer, Genzyme GmbH, Grünenthal GmbH, Mundipharma, Sanofi Pasteur, Medtronic Inc. Neuromodulation, Eisai Co.Ltd., Lilly GmbH, Boehringer Ingelheim Pharma GmbH&Co.KG, Astellas, Desitin, Teva Pharma, Bayer-Schering, MSD GmbH, bioCSL. He has been a consultant for Pfizer, Genzyme GmbH, Grünenthal GmbH, Mundipharma, Allergan, Sanofi Pasteur, Medtronic Inc. Neuromodulation, Eisai Co.Ltd., Lilly GmbH, Boehringer Ingelheim Pharma GmbH&Co.KG, Astellas, Novartis, Bristol-Myers-Squibb, Biogenidec, AstraZeneca, Merck, Abbvie, Daiichi Sankyo, Glenmark Pharmaceuticals, bioCSL, Teva Pharma an Genentech. J.G. has disclosed that she has received speaking fees from Pfizer and travel grants from Pfizer, Grünenthal and Sanofi Pasteur MSD GmbH. She is a consultant for Glenmark Pharma.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

Previous presentation: This report was previously presented at the Meeting of the German Society for Anesthesiology and Intensive Care Medicine, 20 April 2013, as well as shown as a poster at the Meeting of the German Society for the Study of Pain.