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Remifentanil—Acute Opioid Tolerance and Opioid-Induced Hyperalgesia: A Systematic Review

Kim, Sang Hun MD, PhD; Stoicea, Nicoleta MD, PhD; Soghomonyan, Suren MD, PhD; Bergese, Sergio D. MD

American Journal of Therapeutics: May/June 2015 - Volume 22 - Issue 3 - p e62–e74
doi: 10.1097/MJT.0000000000000019
Therapeutic Reviews

The use of opioids may seem to be a double-edged sword; they provide straight analgesic and antihyperalgesic effects initially, but subsequently are associated with the expression of acute opioid tolerance (AOT) and opioid-induced hyperalgesia (OIH) that have been reported in experimental studies and clinical observations. It has been suggested that opioids can induce an acute tolerance and hyperalgesia in dose- and/or time-dependent manners even when used within the clinically accepted doses. Recently, remifentanil has been used for pain management in clinical anesthesia and in the intensive care units because of its rapid onset and offset. We reviewed articles analyzing AOT and/or OIH by remifentanil and focused on the following issues: (1) evidence of remifentanil inducing AOT and/or OIH and (2) importance of AOT and/or OIH in considering the reduction of remifentanil dosage or adopting preventive modulations. Twenty-four experimental and clinical studies were identified using electronic searches of MEDLINE (PubMed, Ovid, Springer, and Elsevier). However, the development of AOT and OIH by remifentanil administration remains controversial. There is no sufficient evidence to support or refute the existence of OIH in humans.

1Department of Anesthesiology and Pain Medicine, School of Medicine, Chosun University, Gwangju, Korea; and

Departments of 2Anesthesiology and

3Neurological Surgery, Ohio State University Medical Center, Columbus, OH.

Address for correspondence: Department of Anesthesiology and Pain Medicine, School of Medicine, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju 501-759, Korea. E-mail:

Supported by a research fund from Chosun University, 2012, and in collaboration with Division of Neuroanesthesia, Department of Anesthesiology, Ohio State University Wexner Medical Center.

The authors have no conflicts of interest to declare.

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