Abstract
Introduction: The use of opioids has been increasing in operating room and intensive care unit to provide perioperative analgesia as well as stable hemodynamics. However, many authors have suggested that the use of opioids is associated with the expression of acute opioid tolerance (AOT) and opioid-induced hyperalgesia (OIH) in experimental studies and clinical observations in dose and/or time dependent exposure even when used within the clinically accepted doses. Recently, remifentanil has been used for pain management during anesthesia as well as in the intensive care units because of its rapid onset and offset.Objectives: Search of the available literature to assess remifentanil AOT and OIH based on available published data.Methods: We reviewed articles analyzing remifentanil AOT and OIH, and focused our literature search on evidence based information. Experimental and clinical studies were identified using electronic searches of Medline (PubMed, Ovid, Springer, and Elsevier, ClinicalKey).Results: Our results showed that the development of remifentanil AOT and OIH is a clinically significant phenomenon requiring further research.Discussions and Conclusions: AOT – defined as an increase in the required opioid dose to maintain adequate analgesia, and OIH – defined as decreased pain threshold after chronic opioid treatment, should be suspected with any unexplained pain report unassociated with the disease progression. The clinical significance of these findings was evaluated taking into account multiple methodological issues including the dose and duration of opioids administration, the different infusion mode, the co-administrated anesthetic drug’s effect, method assessing pain sensitivity, and the repetitive and potentially tissue damaging nature of the stimuli used to determine the threshold during opioid infusion. Future studies need to investigate the contribution of remifentanil induced hyperalgesia to chronic pain and the role of pharmacological modulation to reverse this process.
Highlights
The use of opioids has been increasing in operating room and intensive care unit to provide perioperative analgesia as well as stable hemodynamics
We reviewed articles analyzing remifentanil acute opioid tolerance (AOT) and opioid-induced hyperalgesia (OIH), and focused our literature search on evidence based information
Our results showed that the development of remifentanil AOT and OIH is a clinically significant phenomenon requiring further research
Summary
The use of opioids has been increasing in operating room and intensive care unit to provide perioperative analgesia as well as stable hemodynamics. Even though remifentanil increases analgesia and respiratory depression in a dose-dependent manner (Hughes et al, 1992; Egan et al, 1993; Glass et al, 1993; Westmoreland et al, 1993; Kapila et al, 1995), these effects disappear rapidly after discontinuing administration of the drug because of the extremely short elimination half-life (9.5 ± 4 min). Because of its pharmacodynamic and pharmacokinetic effects, remifentanil has been used in clinical anesthesia as an induction and maintenance agent, and postoperative pain management in the intensive care units. Most of the studies conducted with remifentanil showed cardiovascular responses during perioperative manipulations They recommended a bolus injection of remifentanil of 1 μg/kg as more effective dose in reducing the pressor response during laryngoscopy and tracheal intubation (McAtamney et al, 1998; O’Hare et al, 1999). Remifentanil continuous infusion (CI) can be used for controlling the pain, and the final remifentanil infusion rates have been reported as 0.05–0.26 μg/kg/min for satisfactory www.frontiersin.org
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