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      The analgesic effect of nefopam combined with low dose remifentanil in patients undergoing middle ear surgery under desflurane anesthesia: a randomized controlled trial

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          Abstract

          Background

          We investigated the effects of the combined administration of nefopam, a N-methyl-D-aspartate receptor antagonist and low dose remifentanil, on early postoperative pain and analgesic requirement.

          Methods

          Fifty patients scheduled to undergo mastoidectomy and tympanoplasty were randomized to be given either nefopam 40 mg mixed with normal saline 100 ml (Group N) or an equal amount of normal saline (Group C) before anesthesia induction. Anesthesia was maintained with 5-6 vol% desflurane and remifentanil 0.05-0.15 µg/kg/min during the surgery. Postoperative pain was controlled by titration of ketorolac in the postanesthesia care unit (PACU) and ward. We evaluated the intraoperative remifentanil dose, recovery profiles, ketorolac demand in the PACU and ward, numeric rating scale (NRS) for pain at time intervals of every 10 min for 1 h in the PACU, 6, 12, 18 and 24 h in a ward, as well as the time to first analgesic requirement in the PACU and ward.

          Results

          Ketorolac demand and NRS in the PACU were significantly lower in Group N than Group C (P = 0.002, P = 0.005, respectively). The time to first analgesic requirement in the PACU in Group N were significantly longer than Group C (P = 0.046). There were no significant differences in intraoperative remifentanil dose, ketorolac demand, NRS, and the time to first analgesic requirement in the ward between the groups.

          Conclusions

          Nefopam administration combined with low dose remifentanil infusion reduces pain and analgesic consumption during the immediate postoperative period in patients undergoing middle ear surgery under desflurane anesthesia.

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          Most cited references31

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          Opioid-induced hyperalgesia in humans: molecular mechanisms and clinical considerations.

          Opioid-induced hyperalgesia (OIH) is most broadly defined as a state of nociceptive sensitization caused by exposure to opioids. The state is characterized by a paradoxical response whereby a patient receiving opioids for the treatment of pain may actually become more sensitive to certain painful stimuli. The type of pain experienced may or may not be different from the original underlying painful condition. Although the precise molecular mechanism is not yet understood, it is generally thought to result from neuroplastic changes in the peripheral and central nervous systems that lead to sensitization of pronociceptive pathways. OIH seems to be a distinct, definable, and characteristic phenomenon that may explain loss of opioid efficacy in some cases. Clinicians should suspect expression of OIH when opioid treatment effect seems to wane in the absence of disease progression, particularly if found in the context of unexplained pain reports or diffuse allodynia unassociated with the pain as previously observed. This review highlights the important mechanistic underpinnings and clinical ramifications of OIH and discusses future research directions and the latest clinical evidence for modulation of this potentially troublesome clinical phenomenon.
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            Rapid development of tolerance to analgesia during remifentanil infusion in humans.

            Studies in experimental animals have demonstrated a rapidly developing acute tolerance to the analgesic effect of opioids administered by continuous i.v. infusion. The aim of the present study was to determine whether acute tolerance plays an important role in the analgesic effect of remifentanil provided by i.v. infusion to humans. The analgesic effect of remifentanil, infused at a constant rate of 0.1 microg x kg(-1) x min(-1) for 4 h, was evaluated by measuring pain tolerance with thermal (2 degrees C water) and mechanical (pressure) noxious stimulations in 13 paid volunteers. The constant-rate infusion of remifentanil resulted in a threefold increase in pain tolerance with both tests. After reaching its maximum in 60-90 min, the analgesic effect of remifentanil began to decline despite the constant-rate infusion, and after 3 h of infusion, it was only one fourth of the peak value. A comparative rate in the development of acute tolerance measured in terms of time to 50% recovery during infusion was 129 +/- 27 min (mean +/- SD) with the cold water test and 138 +/- 39 min with the pressure test. We conclude that the development of tolerance should be included in the calculations for target-controlled infusions. Our study shows that tolerance to analgesia during remifentanil infusion is profound and develops very rapidly. The administration of opioids during anesthesia based on target-controlled infusions should include corrections for the development of tolerance.
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              Maintenance anaesthetics during remifentanil-based anaesthesia might affect postoperative pain control after breast cancer surgery.

              Although remifentanil provides profound analgesia during operation, postoperative occurrence of hyperalgesia and tolerance after remifentanil administration could be a challenge to the postoperative pain control. In this investigation, we sought to determine the effect of maintenance with propofol or sevoflurane on postoperative analgesia after remifentanil-based anaesthesia. Two hundred and fourteen women undergoing breast cancer surgery under remifentanil-based general anaesthesia were randomly included in this prospective and double-blind trial. The patients were anaesthetized with sevoflurane (S) or propofol (P) under high (H) or low (L) effect-site concentration (Ce) of remifentanil-based anaesthesia using a target-controlled infusion system; the patients were allocated into the SH, SL, PH, and PL groups. Pain intensity (visual analogue score, VAS) and cumulative morphine requirements were recorded 30 min, 1, 6, 12, and 24 h after operation. The patient characteristics were similar. Cumulative morphine consumption at 24 h after surgery was higher in the SH group [38.6 (sd 14.9)] compared with the SL [31.5 (3.7)], PH [31.7 (8.3)], and PL groups [30.1 (6.1)] (P<0.001). The VAS scores during 24 h after surgery were also higher in the SH group than the SL, PH, and PL groups (P<0.001). Remifentanil hyperalgesia was induced by high dose of remifentanil-based anaesthesia during sevoflurane anaesthesia, whereas that was not apparent during propofol anaesthesia. Also, remifentanil hyperalgesia did not occur during low dose of remifentanil-based anaesthesia. Maintenance of propofol during high-dose remifentanil-based anaesthesia provided better postoperative analgesia.
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                Author and article information

                Journal
                Korean J Anesthesiol
                Korean J Anesthesiol
                KJAE
                Korean Journal of Anesthesiology
                The Korean Society of Anesthesiologists
                2005-6419
                2005-7563
                February 2015
                28 January 2015
                : 68
                : 1
                : 43-49
                Affiliations
                Department of Anesthesiology and Pain Medicine, Guro Hospital, Korea University College of Medicine, Seoul, Korea.
                Author notes
                Corresponding author: Byung Gun Lim, M.D., Ph.D. Department of Anesthesiology and Pain Medicine, Korea University College of Medicine, Guro Hospital, 148, Gurodong-ro, Guro-gu, Seoul 157-703, Korea. Tel: 82-2-2626-1437, Fax: 82-2-851-9897, bglim9205@ 123456korea.ac.kr
                Article
                10.4097/kjae.2015.68.1.43
                4318865
                25664155
                04b75e44-7fdc-44d5-9b77-c098087f585a
                Copyright © the Korean Society of Anesthesiologists, 2015

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 23 May 2014
                : 11 August 2014
                : 08 September 2014
                Categories
                Clinical Research Article

                Anesthesiology & Pain management
                acute opioid tolerance,nefopam,opioid induced hyperalgesia,postoperative pain,remifentanil

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