Cortinez LI, Brandes V, Munoz HR, Guerrero ME, Mur M: No clinical evidence of acute opioid tolerance after remifentanil-based anaesthesia. Br J Anaesth 87: 866-9

University of Santiago, Chile, CiudadSantiago, Santiago Metropolitan, Chile
BJA British Journal of Anaesthesia (Impact Factor: 4.85). 01/2002; 87(6):866-9. DOI: 10.1093/bja/87.6.866
Source: PubMed


We have prospectively assessed whether remifentanil-based anaesthesia is associated with clinically relevant acute opioid tolerance, expressed as greater postoperative pain scores or morphine consumption. Sixty patients undergoing elective gynaecological, non-laparoscopic, surgery were randomly assigned to receive remifentanil (group R, n=30) or sevoflurane (group S, n=30) based anaesthesia. Postoperative analgesia was provided with morphine through a patient-controlled infusion device. Mean (SD) remifentanil infusion rate in group R was 0.23 (0.10) microg kg(-1) min(-1) and mean inspired fraction of sevoflurane in group S was 1.75 (0.70)%. Mean (SD) cumulative morphine consumption during the first 24 postoperative hours was similar between groups: 28.0 (14.2) mg (group R) vs 28.6 (12.4) mg (group S). Pain scores, were also similar between groups during this period. These data do not support the development of acute opioid tolerance after remifentanil-based anaesthesia in this type of surgery.

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    • "However, the clinical significance of these findings, especially in higher dosages used in the intraoperative setting, remains to be studied. In addition, some authors ignored the impact that nitrous oxide might have against the AOT and hyperalgesia (Cortinez et al., 2001; Yeom et al., 2012). Echevarria et al. (2011) reported that the group using the 70% nitrous oxide with remifentanil of 0.3 μg/kg/min showed a greater decreased mechanical threshold than the group without nitrous oxide at postoperative 12–18 h, even though the postoperative pain scores and cumulative morphine consumption was similar between the groups. "
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    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, 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.
    Full-text · Article · May 2014 · Frontiers in Pharmacology
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    • "Morphine is the most widely used narcotic analgesic for relieving severe or chronic pain but its repeated administration leads to a characteristic tolerance (1). Although the clinical importance of opioid tolerance is controversial (2), laboratory studies of this phenomenon have advanced our understanding of analgesic mechanisms in general. On a cellular level, chronic opioid administration was shown to cause spinal changes involving the translocation and activation of protein kinase C and the production of nitric oxide (NO) (3). "
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    ABSTRACT: Glial cells play a critical role in morphine tolerance, resulting from repeated administration of morphine. Both the development and the expression of tolerance are suppressed by the analgesic lamotrigine. This study investigated the relationship between the ability of lamotrigine to maintain the antinociceptive effect of morphine during tolerance development and glial cell activation in the spinal cord. In a rat model, morphine (15 µg) was intrathecally injected once daily for 7 days to induce morphine tolerance. Lamotrigine (200 µg) was co-administered with morphine either for 7 days or the first or last 3 days of this 7 day period. Thermal nociception was measured. OX-42 and GFAP immunoreactivity, indicating spinal microglial and astrocytic activation were evaluated on day 8. Tolerance developed after 7 days of intrathecal morphine administration; however, this was completely blocked and reversed by co-administration of lamotrigine. When lamotrigine was coinjected with morphine on days 5-7, the morphine effect was partially restored. Glial cell activation increased with the development of morphine tolerance but was clearly inhibited in the presence of lamotrigine. These results suggest that, in association with the suppression of spinal glial cell activity, intrathecally coadministered lamotrigine attenuates antinociceptive tolerance to morphine.
    Full-text · Article · Feb 2013 · Journal of Korean medical science
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    • "Patients who self-controlled their analgesia using target-controlled infusions of alfentanil and remifentanil for postoperative analgesia after propofol and remifentanil anesthesia showed no evidence of tolerance to opioids [5]. Studies in patients who underwent elective gynecological non-laparoscopic surgery (average duration, 116 minutes) did not support the theory of the development of acute opioid tolerance after remifentanil-based anesthesia (mean remifentanil infusion rate = 0.23 ± 0.10 µg/kg/min) when compared with sevoflurane-based anesthesia [6]. In a study in which a small-dose of remifentanil (0.08 µg/kg/min) was continuously infused for 3 hours into volunteers, no development of acute opioid tolerance was observed [7]. "
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    ABSTRACT: Although acute tolerance to opioids, especially to remifentanil, has been demonstrated consistently in animal studies, the results of clinical trials in humans are controversial. The aim of this study was to determine whether intraoperative infusions of remifentanil used as an adjuvant in general anesthesia result in acute tolerance, an event manifested by increased postoperative pain and a higher opioid requirement than usual. Sixty patients who underwent surgery under general anesthesia for spinal fusion were randomly assigned to receive sevoflurane-nitrous oxide-oxygen (group SO, n = 20), sevoflurane-remifentanil-nitrous oxide-oxygen (group SR, n = 20), or propofol-remifentanil-oxygen (group PR, n = 20) in a double-blinded manner. All patients within 1 hour after induction received PCA (fentanyl 0.4 µg/kg/ml and ondansetron 16 mg) administered intravenously at a basal infusion rate of 1 ml/h, after being intravenously injected with a loading dose of fentanyl (1 µg/kg). Data for fentanyl requirement, verbal Numerical Rating Scale (NRS) pain score at rest, and presence of nausea or vomiting were collected at 1, 24, and 48 hours after surgery. We did not find any significant difference in postoperative PCA fentanyl requirements, NRS or side effects among the groups. Remifentanil as an adjuvant to sevoflurane or propofol in general anesthesia for adults having surgery for spinal fusion does not appear to cause acute opioid tolerance or hyperalgesia in patients. However, further studies are needed to elucidate whether sevoflurane and propofol exert a clinically significant effect on opioid-induced tolerance or hyperalgesia and whether this effect is related to the age of the patient, the dose and duration of remifentanil given and the intensity of pain experienced postoperatively.
    Full-text · Article · Aug 2012 · Korean journal of anesthesiology
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