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Ignacio Gomez A De Segura - One of the best experts on this subject based on the ideXlab platform.
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Reduction of the sevoflurane Minimum Alveolar Concentration induced by methadone, tramadol, butorphanol and morphine in rats
2020Co-Authors: Mariana Abreu, Javier Benito, Delia Aguado, Ignacio Gomez A De SeguraAbstract:Abstract This study aimed to estimate the reduction in the Minimum Alveolar Concentration (MAC) of sevoflurane induced by low and high doses of methadone (5 and 10 mg/kg), tramadol (25 and 50 mg/kg), butorphanol (5 and 10 mg/kg) or morphine (5 and 10 mg/kg) in the rat. A control group received normal saline. Sixty-three adult male Sprague-Dawley rats were anaesthetized with sevoflurane (n ¼ 7 per group). Sevoflurane MAC was then determined before and after intraperitoneal administration of the opioids or saline. The duration of the sevoflurane MAC reduction and basic cardiovascular and respiratory measurements were also recorded. The baseline MAC was 2.5 (0.3) vol%. Methadone, tramadol and morphine reduced the sevoflurane MAC (low dose: 31 + 10, 38 + 15 and 30 + 13% respectively; high dose: 100 + 0, 83 + 17 and 77 + 25%, respectively) in a dose-dependent manner. The low and high doses of butorphanol reduced the sevoflurane MAC to a similar extent (33 + 7 and 31 + 4%, low and high doses, respectively). Two rats developed apnoea following administration of high-dose butorphanol and methadone. These anaesthetic-sparing effects are clinically relevant and may reduce the adverse effects associated with higher doses of inhalational anaesthetics. Laboratory animals should be administered perioperative analgesics not only for ethical concerns, but also to minimize the impact of pain on physiological parameters and consequently on research results. Opioids reduce the Minimum Alveolar Concentration (MAC) of inhalational anaesthetics, and thus, may reduce undesirable dose-dependent sideeffects, such as cardiorespiratory depression. 1,2 Morphine, buprenorphine, fentanyl and remifentanil have been shown to decrease isoflurane MAC in rats, 3,4 but there are no reports on the effects of methadone, tramadol and butorphanol on the MAC of other inhalational anaesthetics. This disparity may be because the latter anaesthetics are less commonly administered to rats. Methadone, a mu (m)-receptor agonist, differs from classical opioids such as morphine in that it also acts as a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor. 5 Butorphanol is a kappa (k)-receptor agonist with mild antagonistic properties at the m receptor 6 that is used to treat mild pain 7,8 and has a species-dependent effect on the MAC. 9 -13 Tramadol is a synthetic opioid with weak agonist actions at the m opioid receptor, releases serotonin and inhibits the reuptake of norepinephrine. This drug is known to provide pain relief by means of its primary metabolite, O-desmethyl-tramadol. 14,15 Tramadol has been used for analgesic management in the perioperative period in rats, 1 and has been shown to decrease sevoflurane MAC in dogs 19 The MAC of an inhalational anaesthetic is the Concentration required to prevent gross purposeful movement in 50% of subjects in response to a noxious stimulus. This parameter, which is expressed as a percentage at sea-level barometric pressure (760 mmHg)
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amitriptyline minocycline and maropitant reduce the sevoflurane Minimum Alveolar Concentration and potentiate remifentanil but do not prevent acute opioid tolerance and hyperalgesia in the rat a randomised laboratory study
European Journal of Anaesthesiology, 2015Co-Authors: Delia Aguado, Javier Benito, Mariana Abreu, Javier Garciafernandez, Ignacio Gomez A De SeguraAbstract:BACKGROUND The antidepressant amitriptyline, the inhibitor of microglia activation minocycline, and the neurokinin-1 antagonist maropitant have all been used to prevent or treat hyperalgesia and opioid tolerance. OBJECTIVES To determine the effect of amitriptyline, minocycline, maropitant, independently or with remifentanil, on the sevoflurane Minimum Alveolar Concentration in rats and whether these drugs may block opioid-induced hyperalgesia and acute opioid tolerance under inhalational anaesthesia. DESIGN A randomised, laboratory study. SETTING Experimental Unit, La Paz University Hospital, Madrid, Spain. ANIMALS One hundred and fourteen adult male Wistar rats. INTERVENTIONS Intraperitoneal administration of amitriptyline (10 and 50 mg kg-1), minocycline (30 and 100 mg kg-1), maropitant (10 and 30 mg kg-1) or isotonic saline, combined with a constant rate intravenous infusion of remifentanil (240 μg kg-1 h-1) or saline. MAIN OUTCOME MEASURES Sevoflurane Minimum Alveolar Concentration was determined before and after administration of the drugs; acute opioid tolerance was defined as a decreased ability of remifentanil to reduce the Minimum Alveolar Concentration in the short term. In addition, mechanical nociceptive thresholds were determined before and after these treatments. Opioid-induced hyperalgesia was defined as an increase in mechanical nociceptive thresholds after opioid administration. RESULTS Amitriptyline, minocycline and maropitant reduced Minimum Alveolar Concentration up to 24 (8)%, 23 (6)% and 15 (5)%, respectively (P <0.001). Remifentanil alone reduced Minimum Alveolar Concentration by 36 (6)% (P <0.001), and in combination with amitriptyline, minocycline and maropitant, the reduction was 76 (9)%, 75 (16)% and 59 (5)%, respectively (P <0.001). An acute tolerance effect (P < 0.01) and a decrease in the mechanical nociceptive thresholds were observed with remifentanil in all groups. CONCLUSION Amitriptyline, minocycline and maropitant reduced the Minimum Alveolar Concentration and potentiated the remifentanil Minimum Alveolar Concentration reduction but failed to block opioid-induced hyperalgesia and acute opioid tolerance.
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hyperalgesia and increased sevoflurane Minimum Alveolar Concentration induced by opioids in the rat a randomised experimental study
European Journal of Anaesthesiology, 2015Co-Authors: Mariana Abreu, Javier Benito, Delia Aguado, Javier Garciafernandez, Ignacio Gomez A De SeguraAbstract:BACKGROUND Perioperative opioids reduce inhalational anaesthetic requirements. The initial hypoalgesia may, however, be followed by a rebound hyperalgesia. OBJECTIVES To determine whether prior opioid administration influences inhalational anaesthetic requirements, which might be associated with opioid-induced hyperalgesia. DESIGN A prospective, randomised, experimental study. SETTING Experimental Surgery, La Paz University Hospital, Madrid, Spain. ANIMALS Seventy-nine adult male Wistar rats. INTERVENTIONS Sevoflurane Minimum Alveolar Concentration (MAC) and mechanical nociceptive thresholds (MNTs) were assessed at baseline and 7 days later following opioid treatment with remifentanil 120 μg kg-1 h-1, buprenorphine 150 μg kg-1, methadone 8 mg kg-1 or morphine 10 mg kg-1 The duration of the effect of remifentanil on MAC and MNT was evaluated in addition to the preventive effect of ketamine 10 mg kg-1 on remifentanil-induced hyperalgesia. MAIN OUTCOME MEASURES The effect of different opioid treatments on MAC and MNT was evaluated using analysis of variance (ANOVA). RESULTS All studied opioids produced an immediate reduction in sevoflurane MAC, followed by an increase (16%) in baseline MAC 7 days later (P < 0.05), although the immediate MAC reduction produced by these opioids at that time was not different. Remifentanil produced a decrease in MNT (P < 0.05), which was associated with an increase in the MAC (P < 0.05) that persisted at 21 days. The effect of remifentanil on MNT and MAC was blocked by ketamine. CONCLUSION Opioid-induced hyperalgesia was associated with an increase in the MAC in normal rats who had not undergone surgery. Both effects lasted 21 days and were prevented by ketamine.
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reduction of the sevoflurane Minimum Alveolar Concentration induced by methadone tramadol butorphanol and morphine in rats
Laboratory Animals, 2012Co-Authors: Mariana Abreu, Javier Benito, Delia Aguado, Ignacio Gomez A De SeguraAbstract:This study aimed to estimate the reduction in the Minimum Alveolar Concentration (MAC) of sevoflurane induced by low and high doses of methadone (5 and 10 mg/kg), tramadol (25 and 50 mg/kg), butorphanol (5 and 10 mg/kg) or morphine (5 and 10 mg/kg) in the rat. A control group received normal saline. Sixty-three adult male Sprague-Dawley rats were anaesthetized with sevoflurane (n = 7 per group). Sevoflurane MAC was then determined before and after intraperitoneal administration of the opioids or saline. The duration of the sevoflurane MAC reduction and basic cardiovascular and respiratory measurements were also recorded. The baseline MAC was 2.5 (0.3) vol%. Methadone, tramadol and morphine reduced the sevoflurane MAC (low dose: 31 ± 10, 38 ± 15 and 30 ± 13% respectively; high dose: 100 ± 0, 83 ± 17 and 77 ± 25%, respectively) in a dose-dependent manner. The low and high doses of butorphanol reduced the sevoflurane MAC to a similar extent (33 ± 7 and 31 ± 4%, low and high doses, respectively). Two rats developed apnoea following administration of high-dose butorphanol and methadone. These anaesthetic-sparing effects are clinically relevant and may reduce the adverse effects associated with higher doses of inhalational anaesthetics.
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ketamine and remifentanil interactions on the sevoflurane Minimum Alveolar Concentration and acute opioid tolerance in the rat
Anesthesia & Analgesia, 2011Co-Authors: Delia Aguado, Javier Benito, Mariana Abreu, Javier Garciafernandez, Ignacio Gomez A De SeguraAbstract:Background Ketamine is used at low doses for its analgesic and antihyperalgesic properties when combined with opioids but also when opioid-induced hyperalgesia and tolerance appear. In this study we determined the interaction of ketamine and remifentanil on the Minimum Alveolar Concentration (MAC) of sevoflurane in rats and to determine whether ketamine may block acute opioid tolerance (AOT). Methods Male Wistar rats were anesthetized with sevoflurane, and the MAC was determined before and after ketamine administration (10, 20, 40, and 80 mg kg(-1) or saline) alone or combined with remifentanil (120 and 240 μg kg(-1) h(-1), low and high doses, respectively). One additional group received the lowest ketamine dose after starting a remifentanil infusion. Finally, naloxone was administered to determine the potential action of ketamine on opioid receptors. MAC was determined from intratracheal gas samples, and tail clamping was used as a supramaximal stimulus. End-tidal anesthetic Concentrations were assayed using a side stream gas analyzer. Statistical analysis was performed with an analysis of variance. Results Ketamine and remifentanil dose-dependently reduced the MAC. Adding the low dose of remifentanil to ketamine did not improve the MAC reduction, whereas the high dose of remifentanil enhanced ketamine reduction in a subadditive fashion. Nevertheless, ketamine was unable to block the development of AOT to remifentanil at either dose. Finally, naloxone blocked the MAC reduction produced by ketamine. Conclusions A subadditive effect between ketamine and remifentanil was found on the sevoflurane MAC reduction rats. In addition, ketamine was unable to block AOT. The clinical relevance of these findings should be elucidated in future studies to reduce anesthetic requirements.
Delia Aguado - One of the best experts on this subject based on the ideXlab platform.
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Reduction of the sevoflurane Minimum Alveolar Concentration induced by methadone, tramadol, butorphanol and morphine in rats
2020Co-Authors: Mariana Abreu, Javier Benito, Delia Aguado, Ignacio Gomez A De SeguraAbstract:Abstract This study aimed to estimate the reduction in the Minimum Alveolar Concentration (MAC) of sevoflurane induced by low and high doses of methadone (5 and 10 mg/kg), tramadol (25 and 50 mg/kg), butorphanol (5 and 10 mg/kg) or morphine (5 and 10 mg/kg) in the rat. A control group received normal saline. Sixty-three adult male Sprague-Dawley rats were anaesthetized with sevoflurane (n ¼ 7 per group). Sevoflurane MAC was then determined before and after intraperitoneal administration of the opioids or saline. The duration of the sevoflurane MAC reduction and basic cardiovascular and respiratory measurements were also recorded. The baseline MAC was 2.5 (0.3) vol%. Methadone, tramadol and morphine reduced the sevoflurane MAC (low dose: 31 + 10, 38 + 15 and 30 + 13% respectively; high dose: 100 + 0, 83 + 17 and 77 + 25%, respectively) in a dose-dependent manner. The low and high doses of butorphanol reduced the sevoflurane MAC to a similar extent (33 + 7 and 31 + 4%, low and high doses, respectively). Two rats developed apnoea following administration of high-dose butorphanol and methadone. These anaesthetic-sparing effects are clinically relevant and may reduce the adverse effects associated with higher doses of inhalational anaesthetics. Laboratory animals should be administered perioperative analgesics not only for ethical concerns, but also to minimize the impact of pain on physiological parameters and consequently on research results. Opioids reduce the Minimum Alveolar Concentration (MAC) of inhalational anaesthetics, and thus, may reduce undesirable dose-dependent sideeffects, such as cardiorespiratory depression. 1,2 Morphine, buprenorphine, fentanyl and remifentanil have been shown to decrease isoflurane MAC in rats, 3,4 but there are no reports on the effects of methadone, tramadol and butorphanol on the MAC of other inhalational anaesthetics. This disparity may be because the latter anaesthetics are less commonly administered to rats. Methadone, a mu (m)-receptor agonist, differs from classical opioids such as morphine in that it also acts as a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor. 5 Butorphanol is a kappa (k)-receptor agonist with mild antagonistic properties at the m receptor 6 that is used to treat mild pain 7,8 and has a species-dependent effect on the MAC. 9 -13 Tramadol is a synthetic opioid with weak agonist actions at the m opioid receptor, releases serotonin and inhibits the reuptake of norepinephrine. This drug is known to provide pain relief by means of its primary metabolite, O-desmethyl-tramadol. 14,15 Tramadol has been used for analgesic management in the perioperative period in rats, 1 and has been shown to decrease sevoflurane MAC in dogs 19 The MAC of an inhalational anaesthetic is the Concentration required to prevent gross purposeful movement in 50% of subjects in response to a noxious stimulus. This parameter, which is expressed as a percentage at sea-level barometric pressure (760 mmHg)
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The Effects of the Toll-Like Receptor 4 Antagonist, Ibudilast, on Sevoflurane's Minimum Alveolar Concentration and the Delayed Remifentanil-Induced Increase in the Minimum Alveolar Concentration in Rats.
Anesthesia and analgesia, 2016Co-Authors: Daniel Ruiz-pérez, Javier Benito, Gonzalo Polo, Carlota Largo, Delia Aguado, Luis Sanz, Ignacio A. Gómez De SeguraAbstract:BACKGROUND Ultralow doses of naloxone, an opioid and toll-like receptor 4 antagonist, blocked remifentanil-induced hyperalgesia and the associated increase in the Minimum Alveolar Concentration (MAC), but not tolerance. The aim was to determine the effects of the toll-like receptor 4 antagonist, ibudilast, on the MAC in the rat and how it might prevent the effects of remifentanil. METHODS Male Wistar rats were randomly allocated to 5 treatment groups (n = 7 per group): 10 mg/kg ibudilast intraperitoneally, 240 µg/kg/h remifentanil IV, ibudilast plus remifentanil, remifentanil plus naloxone IV, or saline. The sevoflurane MAC was determined 3 times in every rat and every day (days 0, 2, and 4): baseline (MAC-A) and 2 further determinations were made after treatments, 1.5 hours apart (MAC-B and MAC-C). RESULTS A reduction in baseline MAC was produced on day 0 by ibudilast, remifentanil, remifentanil plus ibudilast, remifentanil plus naloxone (P < 0.01), but not saline. Similar effects were found on days 2 and 4. A tolerance to remifentanil was found on days 0, 2, and 4, which neither ibudilast nor naloxone prevented. The MAC increase produced by remifentanil on day 4 (P = 0.001) was prevented by either ibudilast or naloxone. CONCLUSIONS Ibudilast, besides reducing the MAC, prevented the delayed increase in baseline MAC produced by remifentanil but not the increase in MAC caused by tolerance to remifentanil.
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amitriptyline minocycline and maropitant reduce the sevoflurane Minimum Alveolar Concentration and potentiate remifentanil but do not prevent acute opioid tolerance and hyperalgesia in the rat a randomised laboratory study
European Journal of Anaesthesiology, 2015Co-Authors: Delia Aguado, Javier Benito, Mariana Abreu, Javier Garciafernandez, Ignacio Gomez A De SeguraAbstract:BACKGROUND The antidepressant amitriptyline, the inhibitor of microglia activation minocycline, and the neurokinin-1 antagonist maropitant have all been used to prevent or treat hyperalgesia and opioid tolerance. OBJECTIVES To determine the effect of amitriptyline, minocycline, maropitant, independently or with remifentanil, on the sevoflurane Minimum Alveolar Concentration in rats and whether these drugs may block opioid-induced hyperalgesia and acute opioid tolerance under inhalational anaesthesia. DESIGN A randomised, laboratory study. SETTING Experimental Unit, La Paz University Hospital, Madrid, Spain. ANIMALS One hundred and fourteen adult male Wistar rats. INTERVENTIONS Intraperitoneal administration of amitriptyline (10 and 50 mg kg-1), minocycline (30 and 100 mg kg-1), maropitant (10 and 30 mg kg-1) or isotonic saline, combined with a constant rate intravenous infusion of remifentanil (240 μg kg-1 h-1) or saline. MAIN OUTCOME MEASURES Sevoflurane Minimum Alveolar Concentration was determined before and after administration of the drugs; acute opioid tolerance was defined as a decreased ability of remifentanil to reduce the Minimum Alveolar Concentration in the short term. In addition, mechanical nociceptive thresholds were determined before and after these treatments. Opioid-induced hyperalgesia was defined as an increase in mechanical nociceptive thresholds after opioid administration. RESULTS Amitriptyline, minocycline and maropitant reduced Minimum Alveolar Concentration up to 24 (8)%, 23 (6)% and 15 (5)%, respectively (P <0.001). Remifentanil alone reduced Minimum Alveolar Concentration by 36 (6)% (P <0.001), and in combination with amitriptyline, minocycline and maropitant, the reduction was 76 (9)%, 75 (16)% and 59 (5)%, respectively (P <0.001). An acute tolerance effect (P < 0.01) and a decrease in the mechanical nociceptive thresholds were observed with remifentanil in all groups. CONCLUSION Amitriptyline, minocycline and maropitant reduced the Minimum Alveolar Concentration and potentiated the remifentanil Minimum Alveolar Concentration reduction but failed to block opioid-induced hyperalgesia and acute opioid tolerance.
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hyperalgesia and increased sevoflurane Minimum Alveolar Concentration induced by opioids in the rat a randomised experimental study
European Journal of Anaesthesiology, 2015Co-Authors: Mariana Abreu, Javier Benito, Delia Aguado, Javier Garciafernandez, Ignacio Gomez A De SeguraAbstract:BACKGROUND Perioperative opioids reduce inhalational anaesthetic requirements. The initial hypoalgesia may, however, be followed by a rebound hyperalgesia. OBJECTIVES To determine whether prior opioid administration influences inhalational anaesthetic requirements, which might be associated with opioid-induced hyperalgesia. DESIGN A prospective, randomised, experimental study. SETTING Experimental Surgery, La Paz University Hospital, Madrid, Spain. ANIMALS Seventy-nine adult male Wistar rats. INTERVENTIONS Sevoflurane Minimum Alveolar Concentration (MAC) and mechanical nociceptive thresholds (MNTs) were assessed at baseline and 7 days later following opioid treatment with remifentanil 120 μg kg-1 h-1, buprenorphine 150 μg kg-1, methadone 8 mg kg-1 or morphine 10 mg kg-1 The duration of the effect of remifentanil on MAC and MNT was evaluated in addition to the preventive effect of ketamine 10 mg kg-1 on remifentanil-induced hyperalgesia. MAIN OUTCOME MEASURES The effect of different opioid treatments on MAC and MNT was evaluated using analysis of variance (ANOVA). RESULTS All studied opioids produced an immediate reduction in sevoflurane MAC, followed by an increase (16%) in baseline MAC 7 days later (P < 0.05), although the immediate MAC reduction produced by these opioids at that time was not different. Remifentanil produced a decrease in MNT (P < 0.05), which was associated with an increase in the MAC (P < 0.05) that persisted at 21 days. The effect of remifentanil on MNT and MAC was blocked by ketamine. CONCLUSION Opioid-induced hyperalgesia was associated with an increase in the MAC in normal rats who had not undergone surgery. Both effects lasted 21 days and were prevented by ketamine.
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reduction of the sevoflurane Minimum Alveolar Concentration induced by methadone tramadol butorphanol and morphine in rats
Laboratory Animals, 2012Co-Authors: Mariana Abreu, Javier Benito, Delia Aguado, Ignacio Gomez A De SeguraAbstract:This study aimed to estimate the reduction in the Minimum Alveolar Concentration (MAC) of sevoflurane induced by low and high doses of methadone (5 and 10 mg/kg), tramadol (25 and 50 mg/kg), butorphanol (5 and 10 mg/kg) or morphine (5 and 10 mg/kg) in the rat. A control group received normal saline. Sixty-three adult male Sprague-Dawley rats were anaesthetized with sevoflurane (n = 7 per group). Sevoflurane MAC was then determined before and after intraperitoneal administration of the opioids or saline. The duration of the sevoflurane MAC reduction and basic cardiovascular and respiratory measurements were also recorded. The baseline MAC was 2.5 (0.3) vol%. Methadone, tramadol and morphine reduced the sevoflurane MAC (low dose: 31 ± 10, 38 ± 15 and 30 ± 13% respectively; high dose: 100 ± 0, 83 ± 17 and 77 ± 25%, respectively) in a dose-dependent manner. The low and high doses of butorphanol reduced the sevoflurane MAC to a similar extent (33 ± 7 and 31 ± 4%, low and high doses, respectively). Two rats developed apnoea following administration of high-dose butorphanol and methadone. These anaesthetic-sparing effects are clinically relevant and may reduce the adverse effects associated with higher doses of inhalational anaesthetics.
Edmond I. Eger - One of the best experts on this subject based on the ideXlab platform.
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alterations in spinal but not cerebral cerebrospinal fluid na Concentrations affect the isoflurane Minimum Alveolar Concentration in rats
Anesthesia & Analgesia, 2007Co-Authors: Michael J. Laster, Edmond I. Eger, Yi Zhang, Dimitry Shnayderman, James M SonnerAbstract:BACKGROUND: Previous studies demonstrated that MAC (the Minimum Alveolar Concentration of an inhaled anesthetic that produces immobility in 50% of subjects exposed to noxious stimulation) for halothane directly correlates with the central nervous system Concentration of Na + . However, those studies globally altered Na + Concentrations, and thus did not distinguish effects on the spinal cord from cerebral effects. This is an important distinction because the cord appears to be the primary site for mediation of the immobility produced by inhaled anesthetics. Accordingly, in the present study, we examined the effect of altering intrathecal versus intracerebroventricular Concentrations of Na + on MAC. METHODS: In rats prepared with chronic indwelling catheters or stylets, we infused solutions deficient in Na + and with an excess of Na + into the lumbar subarachnoid and intracerebroventricular spaces and measured MAC for isoflurane before, during, and after infusion. RESULTS: MAC of isoflurane correlated directly with Concentrations of Na + infused intrathecally but did not correlate with Concentrations infused intracerebroventricularly. CONCLUSION: The results are consistent with a mediation or modulation of MAC by Na + channels. These might include voltage-gated or ligand-gated channels or other Na-sensitive targets (e.g., pumps, transporters, exchangers).
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do n methyl d aspartate receptors mediate the capacity of inhaled anesthetics to suppress the temporal summation that contributes to Minimum Alveolar Concentration
Anesthesia & Analgesia, 2006Co-Authors: Robert C. Dutton, Douglas E Raines, James M Sonner, Ken Solt, Michael J. Laster, Yilei Xing, Edmond I. EgerAbstract:Antagonism of N-methyl-d-aspartate (NMDA) receptors markedly decreases the Minimum Alveolar Concentration (MAC) of inhaled anesthetics. To assess the importance of suppression of the temporal summation NMDA receptor component of MAC, we stimulated the tail of rats with trains of electrical pulses of varying interstimulus intervals (ISIs) and determined the inhaled anesthetic Concentrations (crossover Concentrations) that suppressed movement at different ISIs. The slopes of crossover Concentrations versus ISIs provided a measure of temporal summation for each anesthetic. We studied five anesthetics that differ widely in their in vitro capacity to block NMDA receptors. To block NMDA receptor transmission and reveal the NMDA receptor component, the NMDA receptor antagonist, MK801, was separately added during each anesthetic. Halothane, isoflurane, and hexafluorobenzene did not appreciably suppress the NMDA receptor components of temporal summation, which contributed to 21% to 29% of MAC (P < 0.05 for each). Xenon and o-difluorobenzene suppressed these components to 8% to 0%, respectively, of MAC (neither significant), consistent with their greater NMDA receptor blocking action in vitro. NMDA receptor blockade may contribute to the MAC produced by inhaled anesthetics that potently inhibit NMDA receptors in vitro but not those that have a limited in vitro effect.
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women appear to have the same Minimum Alveolar Concentration as men a retrospective study
Anesthesiology, 2003Co-Authors: Edmond I. Eger, Takasumi Katoh, Michael J. Laster, George A Gregory, James M SonnerAbstract:Background: A recent report finds that elderly Japanese women given xenon have a significantly smaller (26% less) MAC (Minimum Alveolar Concentration required to eliminate movement in response to surgical incision in 50% of patients) than Japanese men of the same age. The authors assessed whether this finding applied to other/all anesthetics. Methods: The authors reviewed data obtained previously for 258 patients (127 women and 131 men) anesthetized with desflurane, diethyl ether, halothane, methoxyflurane, sevoflurane, or xenon. Data were normalized to the MAC for the anesthetic as determined by logistic regression (i.e., MAC would equal a value of 1.000.) Results: The MAC for the normalized combined (all) data for women (1.013 0.017; mean SEM) did not differ significantly from the normalized combined data for men (1.005 0.009), and neither differed significantly from 1.000. However, a significantly smaller MAC value was found for women in two studies of sevoflurane (subsets of the above studies) given to Japanese patients: 12% in one study and 16% in the other. Conclusions: Overall, no difference in MAC was found for women versus men. Whether women (particularly older Japanese women) have a smaller MAC than men remains to be confirmed by prospective studies.
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temporal summation governs part of the Minimum Alveolar Concentration of isoflurane anesthesia
Anesthesiology, 2003Co-Authors: Robert C. Dutton, James M Sonner, Michael J. Laster, Yi Zhang, Caroline R Stabernack, Edmond I. EgerAbstract:Background: General anesthesia may delay the onset of movement in response to noxious stimulation. The authors hypothesized that the production of immobility could involve depression of time-related processes involved in the generation of movement. Methods: The delays (latencies) between onset of tail clamp (n 16) or 50-Hz continuous electrical stimulation (n 8) and movement were measured in rats equilibrated at 0.1– 0.2% increasing steps of isoflurane. In other rats (n 8), the isoflurane Concentrations just permitting and preventing movement (crossover Concentrations) in response to trains of 0.5-ms 50-V square-wave pulses of interstimulus intervals of 10, 3, 1, 0.3, or 0.1 s during the step increases were measured. These measures were again made during administration of intravenous MK801, an N-methyl-D-aspartate receptor antagonist that can block temporal summation (n 6). Temporal summation refers to the cumulative effect of repeated stimuli. Crossover Concentrations to 10- and 0.1-s interstimulus interval pulses ranging in voltage from 0.25–50 V were also measured (n 4). Results: The increase in Concentrations from 0.6 to nearly 1.0 Minimum Alveolar Concentration progressively increased latency from less tha n1st o 58 s.Shortening the interstimulus interval (50 V) pulses from 10 to 0.1 s progressively increased crossover Concentrations from 0.6 to 1.0 Minimum Alveolar Concentration. In contrast, during MK801 administration shortening interstimulus intervals did not change crossover Concentrations, producing a flat response to change in the interstimulus interval. Increasing the voltage of interstimulus interval pulses increased the crossover Concentrations but did not change the response to change in interstimulus intervals for pulses greater than 1 V. Conclusions: Increasing the duration or frequency (interstimulus interval) of stimulation increases the Concentration of isoflurane required to suppress movement by a 0.4 Minimum Alveolar Concentration MK801 blocks this effect, a finding consistent with temporal summation (which requires intact N-methyl-D-aspartate receptor activity) at Concentrations of up to 1 Minimum Alveolar Concentration isoflurane. THE mechanical or electrical stimulation used to determine MAC (the Minimum Alveolar Concentration producing immobility in 50% of subjects receiving noxious stimulation) is applied continuously for up to 1 min. 1–5 This period allows for a delay between the onset of stimulation and the beginning of movement. The delay seems to increase as the anesthetic Concentration approaches MAC, suggesting that time-related processes underlie the generation of the movement and that increasing anesthetic Concentrations are required to suppress the response to increasing durations of stimulation. Such processes may be assessed by application of temporally graded electrical stimuli of the type used to create neuronal windup. 6 –10 Typically, these stimuli are trains of brief (0.5 ms) high-intensity square-wave pulses with relatively large interstimulus intervals (ISI), often up to 3 s. Such stimuli delivered to spinal cord afferents of spinal cord-transected rats can produce a cumulative depolarization of dorsal and ventral horn neurons. After several seconds, this progressive depolarization can reach a threshold, triggering a sustained burst of action potentials, giving rise to the term “windup.” N-methyl-Daspartate (NMDA) receptor activity underlies at least part of the cumulative depolarization and subsequent windup. 11,12 We hypothesized that temporal summation, the cumulative effect of repeated stimulation, might govern part of the MAC for isoflurane anesthesia. Although electrophysiologic and electromyographic effects of temporal summation have been investigated during isoflurane and halothane anesthesia in humans and rodents, 13–16 the involvement of temporal summation in the generation of movement during anesthesia has not been investigated. To document the time-related dose-dependent effect of isoflurane on the generation of movement responses, we measured the latency to movement after tail clamp and 50-Hz continuous stimulation. To test for temporal summation, we measured the effect of the ISI on the latency to movement responses, on the Concentrations required to achieve immobility, and on the observed buildup of muscle tone and hindlimb electromyogram. To determine if disruption of temporal summation impaired the generation of movement, we measured the effect of the NMDA antagonist, MK801, on isoflurane Concentrations required to achieve immobility during the ISI pulses. To study the dose-dependent effect of isoflurane on temporal summation, we studied the effect of ISIs of increasing voltage and the corresponding increasing Concentrations required to achieve immobility.
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a brief history of the origin of Minimum Alveolar Concentration mac
Anesthesiology, 2002Co-Authors: Edmond I. EgerAbstract:Minimum Alveolar anesthetic Concentration: A standard of anesthetic potency. By Eger EI II, Saidman LJ, Brandstater B. Anesthesiology 1965; 26:756–63.The Minimum Alveolar Concentration of anesthetic (MAC) necessary to prevent movement in response to a painful stimulus was relatively constant in dogs
Javier Benito - One of the best experts on this subject based on the ideXlab platform.
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Reduction of the sevoflurane Minimum Alveolar Concentration induced by methadone, tramadol, butorphanol and morphine in rats
2020Co-Authors: Mariana Abreu, Javier Benito, Delia Aguado, Ignacio Gomez A De SeguraAbstract:Abstract This study aimed to estimate the reduction in the Minimum Alveolar Concentration (MAC) of sevoflurane induced by low and high doses of methadone (5 and 10 mg/kg), tramadol (25 and 50 mg/kg), butorphanol (5 and 10 mg/kg) or morphine (5 and 10 mg/kg) in the rat. A control group received normal saline. Sixty-three adult male Sprague-Dawley rats were anaesthetized with sevoflurane (n ¼ 7 per group). Sevoflurane MAC was then determined before and after intraperitoneal administration of the opioids or saline. The duration of the sevoflurane MAC reduction and basic cardiovascular and respiratory measurements were also recorded. The baseline MAC was 2.5 (0.3) vol%. Methadone, tramadol and morphine reduced the sevoflurane MAC (low dose: 31 + 10, 38 + 15 and 30 + 13% respectively; high dose: 100 + 0, 83 + 17 and 77 + 25%, respectively) in a dose-dependent manner. The low and high doses of butorphanol reduced the sevoflurane MAC to a similar extent (33 + 7 and 31 + 4%, low and high doses, respectively). Two rats developed apnoea following administration of high-dose butorphanol and methadone. These anaesthetic-sparing effects are clinically relevant and may reduce the adverse effects associated with higher doses of inhalational anaesthetics. Laboratory animals should be administered perioperative analgesics not only for ethical concerns, but also to minimize the impact of pain on physiological parameters and consequently on research results. Opioids reduce the Minimum Alveolar Concentration (MAC) of inhalational anaesthetics, and thus, may reduce undesirable dose-dependent sideeffects, such as cardiorespiratory depression. 1,2 Morphine, buprenorphine, fentanyl and remifentanil have been shown to decrease isoflurane MAC in rats, 3,4 but there are no reports on the effects of methadone, tramadol and butorphanol on the MAC of other inhalational anaesthetics. This disparity may be because the latter anaesthetics are less commonly administered to rats. Methadone, a mu (m)-receptor agonist, differs from classical opioids such as morphine in that it also acts as a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor. 5 Butorphanol is a kappa (k)-receptor agonist with mild antagonistic properties at the m receptor 6 that is used to treat mild pain 7,8 and has a species-dependent effect on the MAC. 9 -13 Tramadol is a synthetic opioid with weak agonist actions at the m opioid receptor, releases serotonin and inhibits the reuptake of norepinephrine. This drug is known to provide pain relief by means of its primary metabolite, O-desmethyl-tramadol. 14,15 Tramadol has been used for analgesic management in the perioperative period in rats, 1 and has been shown to decrease sevoflurane MAC in dogs 19 The MAC of an inhalational anaesthetic is the Concentration required to prevent gross purposeful movement in 50% of subjects in response to a noxious stimulus. This parameter, which is expressed as a percentage at sea-level barometric pressure (760 mmHg)
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The Effects of the Toll-Like Receptor 4 Antagonist, Ibudilast, on Sevoflurane's Minimum Alveolar Concentration and the Delayed Remifentanil-Induced Increase in the Minimum Alveolar Concentration in Rats.
Anesthesia and analgesia, 2016Co-Authors: Daniel Ruiz-pérez, Javier Benito, Gonzalo Polo, Carlota Largo, Delia Aguado, Luis Sanz, Ignacio A. Gómez De SeguraAbstract:BACKGROUND Ultralow doses of naloxone, an opioid and toll-like receptor 4 antagonist, blocked remifentanil-induced hyperalgesia and the associated increase in the Minimum Alveolar Concentration (MAC), but not tolerance. The aim was to determine the effects of the toll-like receptor 4 antagonist, ibudilast, on the MAC in the rat and how it might prevent the effects of remifentanil. METHODS Male Wistar rats were randomly allocated to 5 treatment groups (n = 7 per group): 10 mg/kg ibudilast intraperitoneally, 240 µg/kg/h remifentanil IV, ibudilast plus remifentanil, remifentanil plus naloxone IV, or saline. The sevoflurane MAC was determined 3 times in every rat and every day (days 0, 2, and 4): baseline (MAC-A) and 2 further determinations were made after treatments, 1.5 hours apart (MAC-B and MAC-C). RESULTS A reduction in baseline MAC was produced on day 0 by ibudilast, remifentanil, remifentanil plus ibudilast, remifentanil plus naloxone (P < 0.01), but not saline. Similar effects were found on days 2 and 4. A tolerance to remifentanil was found on days 0, 2, and 4, which neither ibudilast nor naloxone prevented. The MAC increase produced by remifentanil on day 4 (P = 0.001) was prevented by either ibudilast or naloxone. CONCLUSIONS Ibudilast, besides reducing the MAC, prevented the delayed increase in baseline MAC produced by remifentanil but not the increase in MAC caused by tolerance to remifentanil.
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amitriptyline minocycline and maropitant reduce the sevoflurane Minimum Alveolar Concentration and potentiate remifentanil but do not prevent acute opioid tolerance and hyperalgesia in the rat a randomised laboratory study
European Journal of Anaesthesiology, 2015Co-Authors: Delia Aguado, Javier Benito, Mariana Abreu, Javier Garciafernandez, Ignacio Gomez A De SeguraAbstract:BACKGROUND The antidepressant amitriptyline, the inhibitor of microglia activation minocycline, and the neurokinin-1 antagonist maropitant have all been used to prevent or treat hyperalgesia and opioid tolerance. OBJECTIVES To determine the effect of amitriptyline, minocycline, maropitant, independently or with remifentanil, on the sevoflurane Minimum Alveolar Concentration in rats and whether these drugs may block opioid-induced hyperalgesia and acute opioid tolerance under inhalational anaesthesia. DESIGN A randomised, laboratory study. SETTING Experimental Unit, La Paz University Hospital, Madrid, Spain. ANIMALS One hundred and fourteen adult male Wistar rats. INTERVENTIONS Intraperitoneal administration of amitriptyline (10 and 50 mg kg-1), minocycline (30 and 100 mg kg-1), maropitant (10 and 30 mg kg-1) or isotonic saline, combined with a constant rate intravenous infusion of remifentanil (240 μg kg-1 h-1) or saline. MAIN OUTCOME MEASURES Sevoflurane Minimum Alveolar Concentration was determined before and after administration of the drugs; acute opioid tolerance was defined as a decreased ability of remifentanil to reduce the Minimum Alveolar Concentration in the short term. In addition, mechanical nociceptive thresholds were determined before and after these treatments. Opioid-induced hyperalgesia was defined as an increase in mechanical nociceptive thresholds after opioid administration. RESULTS Amitriptyline, minocycline and maropitant reduced Minimum Alveolar Concentration up to 24 (8)%, 23 (6)% and 15 (5)%, respectively (P <0.001). Remifentanil alone reduced Minimum Alveolar Concentration by 36 (6)% (P <0.001), and in combination with amitriptyline, minocycline and maropitant, the reduction was 76 (9)%, 75 (16)% and 59 (5)%, respectively (P <0.001). An acute tolerance effect (P < 0.01) and a decrease in the mechanical nociceptive thresholds were observed with remifentanil in all groups. CONCLUSION Amitriptyline, minocycline and maropitant reduced the Minimum Alveolar Concentration and potentiated the remifentanil Minimum Alveolar Concentration reduction but failed to block opioid-induced hyperalgesia and acute opioid tolerance.
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hyperalgesia and increased sevoflurane Minimum Alveolar Concentration induced by opioids in the rat a randomised experimental study
European Journal of Anaesthesiology, 2015Co-Authors: Mariana Abreu, Javier Benito, Delia Aguado, Javier Garciafernandez, Ignacio Gomez A De SeguraAbstract:BACKGROUND Perioperative opioids reduce inhalational anaesthetic requirements. The initial hypoalgesia may, however, be followed by a rebound hyperalgesia. OBJECTIVES To determine whether prior opioid administration influences inhalational anaesthetic requirements, which might be associated with opioid-induced hyperalgesia. DESIGN A prospective, randomised, experimental study. SETTING Experimental Surgery, La Paz University Hospital, Madrid, Spain. ANIMALS Seventy-nine adult male Wistar rats. INTERVENTIONS Sevoflurane Minimum Alveolar Concentration (MAC) and mechanical nociceptive thresholds (MNTs) were assessed at baseline and 7 days later following opioid treatment with remifentanil 120 μg kg-1 h-1, buprenorphine 150 μg kg-1, methadone 8 mg kg-1 or morphine 10 mg kg-1 The duration of the effect of remifentanil on MAC and MNT was evaluated in addition to the preventive effect of ketamine 10 mg kg-1 on remifentanil-induced hyperalgesia. MAIN OUTCOME MEASURES The effect of different opioid treatments on MAC and MNT was evaluated using analysis of variance (ANOVA). RESULTS All studied opioids produced an immediate reduction in sevoflurane MAC, followed by an increase (16%) in baseline MAC 7 days later (P < 0.05), although the immediate MAC reduction produced by these opioids at that time was not different. Remifentanil produced a decrease in MNT (P < 0.05), which was associated with an increase in the MAC (P < 0.05) that persisted at 21 days. The effect of remifentanil on MNT and MAC was blocked by ketamine. CONCLUSION Opioid-induced hyperalgesia was associated with an increase in the MAC in normal rats who had not undergone surgery. Both effects lasted 21 days and were prevented by ketamine.
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reduction of the sevoflurane Minimum Alveolar Concentration induced by methadone tramadol butorphanol and morphine in rats
Laboratory Animals, 2012Co-Authors: Mariana Abreu, Javier Benito, Delia Aguado, Ignacio Gomez A De SeguraAbstract:This study aimed to estimate the reduction in the Minimum Alveolar Concentration (MAC) of sevoflurane induced by low and high doses of methadone (5 and 10 mg/kg), tramadol (25 and 50 mg/kg), butorphanol (5 and 10 mg/kg) or morphine (5 and 10 mg/kg) in the rat. A control group received normal saline. Sixty-three adult male Sprague-Dawley rats were anaesthetized with sevoflurane (n = 7 per group). Sevoflurane MAC was then determined before and after intraperitoneal administration of the opioids or saline. The duration of the sevoflurane MAC reduction and basic cardiovascular and respiratory measurements were also recorded. The baseline MAC was 2.5 (0.3) vol%. Methadone, tramadol and morphine reduced the sevoflurane MAC (low dose: 31 ± 10, 38 ± 15 and 30 ± 13% respectively; high dose: 100 ± 0, 83 ± 17 and 77 ± 25%, respectively) in a dose-dependent manner. The low and high doses of butorphanol reduced the sevoflurane MAC to a similar extent (33 ± 7 and 31 ± 4%, low and high doses, respectively). Two rats developed apnoea following administration of high-dose butorphanol and methadone. These anaesthetic-sparing effects are clinically relevant and may reduce the adverse effects associated with higher doses of inhalational anaesthetics.
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Reduction of the sevoflurane Minimum Alveolar Concentration induced by methadone, tramadol, butorphanol and morphine in rats
2020Co-Authors: Mariana Abreu, Javier Benito, Delia Aguado, Ignacio Gomez A De SeguraAbstract:Abstract This study aimed to estimate the reduction in the Minimum Alveolar Concentration (MAC) of sevoflurane induced by low and high doses of methadone (5 and 10 mg/kg), tramadol (25 and 50 mg/kg), butorphanol (5 and 10 mg/kg) or morphine (5 and 10 mg/kg) in the rat. A control group received normal saline. Sixty-three adult male Sprague-Dawley rats were anaesthetized with sevoflurane (n ¼ 7 per group). Sevoflurane MAC was then determined before and after intraperitoneal administration of the opioids or saline. The duration of the sevoflurane MAC reduction and basic cardiovascular and respiratory measurements were also recorded. The baseline MAC was 2.5 (0.3) vol%. Methadone, tramadol and morphine reduced the sevoflurane MAC (low dose: 31 + 10, 38 + 15 and 30 + 13% respectively; high dose: 100 + 0, 83 + 17 and 77 + 25%, respectively) in a dose-dependent manner. The low and high doses of butorphanol reduced the sevoflurane MAC to a similar extent (33 + 7 and 31 + 4%, low and high doses, respectively). Two rats developed apnoea following administration of high-dose butorphanol and methadone. These anaesthetic-sparing effects are clinically relevant and may reduce the adverse effects associated with higher doses of inhalational anaesthetics. Laboratory animals should be administered perioperative analgesics not only for ethical concerns, but also to minimize the impact of pain on physiological parameters and consequently on research results. Opioids reduce the Minimum Alveolar Concentration (MAC) of inhalational anaesthetics, and thus, may reduce undesirable dose-dependent sideeffects, such as cardiorespiratory depression. 1,2 Morphine, buprenorphine, fentanyl and remifentanil have been shown to decrease isoflurane MAC in rats, 3,4 but there are no reports on the effects of methadone, tramadol and butorphanol on the MAC of other inhalational anaesthetics. This disparity may be because the latter anaesthetics are less commonly administered to rats. Methadone, a mu (m)-receptor agonist, differs from classical opioids such as morphine in that it also acts as a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor. 5 Butorphanol is a kappa (k)-receptor agonist with mild antagonistic properties at the m receptor 6 that is used to treat mild pain 7,8 and has a species-dependent effect on the MAC. 9 -13 Tramadol is a synthetic opioid with weak agonist actions at the m opioid receptor, releases serotonin and inhibits the reuptake of norepinephrine. This drug is known to provide pain relief by means of its primary metabolite, O-desmethyl-tramadol. 14,15 Tramadol has been used for analgesic management in the perioperative period in rats, 1 and has been shown to decrease sevoflurane MAC in dogs 19 The MAC of an inhalational anaesthetic is the Concentration required to prevent gross purposeful movement in 50% of subjects in response to a noxious stimulus. This parameter, which is expressed as a percentage at sea-level barometric pressure (760 mmHg)
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amitriptyline minocycline and maropitant reduce the sevoflurane Minimum Alveolar Concentration and potentiate remifentanil but do not prevent acute opioid tolerance and hyperalgesia in the rat a randomised laboratory study
European Journal of Anaesthesiology, 2015Co-Authors: Delia Aguado, Javier Benito, Mariana Abreu, Javier Garciafernandez, Ignacio Gomez A De SeguraAbstract:BACKGROUND The antidepressant amitriptyline, the inhibitor of microglia activation minocycline, and the neurokinin-1 antagonist maropitant have all been used to prevent or treat hyperalgesia and opioid tolerance. OBJECTIVES To determine the effect of amitriptyline, minocycline, maropitant, independently or with remifentanil, on the sevoflurane Minimum Alveolar Concentration in rats and whether these drugs may block opioid-induced hyperalgesia and acute opioid tolerance under inhalational anaesthesia. DESIGN A randomised, laboratory study. SETTING Experimental Unit, La Paz University Hospital, Madrid, Spain. ANIMALS One hundred and fourteen adult male Wistar rats. INTERVENTIONS Intraperitoneal administration of amitriptyline (10 and 50 mg kg-1), minocycline (30 and 100 mg kg-1), maropitant (10 and 30 mg kg-1) or isotonic saline, combined with a constant rate intravenous infusion of remifentanil (240 μg kg-1 h-1) or saline. MAIN OUTCOME MEASURES Sevoflurane Minimum Alveolar Concentration was determined before and after administration of the drugs; acute opioid tolerance was defined as a decreased ability of remifentanil to reduce the Minimum Alveolar Concentration in the short term. In addition, mechanical nociceptive thresholds were determined before and after these treatments. Opioid-induced hyperalgesia was defined as an increase in mechanical nociceptive thresholds after opioid administration. RESULTS Amitriptyline, minocycline and maropitant reduced Minimum Alveolar Concentration up to 24 (8)%, 23 (6)% and 15 (5)%, respectively (P <0.001). Remifentanil alone reduced Minimum Alveolar Concentration by 36 (6)% (P <0.001), and in combination with amitriptyline, minocycline and maropitant, the reduction was 76 (9)%, 75 (16)% and 59 (5)%, respectively (P <0.001). An acute tolerance effect (P < 0.01) and a decrease in the mechanical nociceptive thresholds were observed with remifentanil in all groups. CONCLUSION Amitriptyline, minocycline and maropitant reduced the Minimum Alveolar Concentration and potentiated the remifentanil Minimum Alveolar Concentration reduction but failed to block opioid-induced hyperalgesia and acute opioid tolerance.
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hyperalgesia and increased sevoflurane Minimum Alveolar Concentration induced by opioids in the rat a randomised experimental study
European Journal of Anaesthesiology, 2015Co-Authors: Mariana Abreu, Javier Benito, Delia Aguado, Javier Garciafernandez, Ignacio Gomez A De SeguraAbstract:BACKGROUND Perioperative opioids reduce inhalational anaesthetic requirements. The initial hypoalgesia may, however, be followed by a rebound hyperalgesia. OBJECTIVES To determine whether prior opioid administration influences inhalational anaesthetic requirements, which might be associated with opioid-induced hyperalgesia. DESIGN A prospective, randomised, experimental study. SETTING Experimental Surgery, La Paz University Hospital, Madrid, Spain. ANIMALS Seventy-nine adult male Wistar rats. INTERVENTIONS Sevoflurane Minimum Alveolar Concentration (MAC) and mechanical nociceptive thresholds (MNTs) were assessed at baseline and 7 days later following opioid treatment with remifentanil 120 μg kg-1 h-1, buprenorphine 150 μg kg-1, methadone 8 mg kg-1 or morphine 10 mg kg-1 The duration of the effect of remifentanil on MAC and MNT was evaluated in addition to the preventive effect of ketamine 10 mg kg-1 on remifentanil-induced hyperalgesia. MAIN OUTCOME MEASURES The effect of different opioid treatments on MAC and MNT was evaluated using analysis of variance (ANOVA). RESULTS All studied opioids produced an immediate reduction in sevoflurane MAC, followed by an increase (16%) in baseline MAC 7 days later (P < 0.05), although the immediate MAC reduction produced by these opioids at that time was not different. Remifentanil produced a decrease in MNT (P < 0.05), which was associated with an increase in the MAC (P < 0.05) that persisted at 21 days. The effect of remifentanil on MNT and MAC was blocked by ketamine. CONCLUSION Opioid-induced hyperalgesia was associated with an increase in the MAC in normal rats who had not undergone surgery. Both effects lasted 21 days and were prevented by ketamine.
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reduction of the sevoflurane Minimum Alveolar Concentration induced by methadone tramadol butorphanol and morphine in rats
Laboratory Animals, 2012Co-Authors: Mariana Abreu, Javier Benito, Delia Aguado, Ignacio Gomez A De SeguraAbstract:This study aimed to estimate the reduction in the Minimum Alveolar Concentration (MAC) of sevoflurane induced by low and high doses of methadone (5 and 10 mg/kg), tramadol (25 and 50 mg/kg), butorphanol (5 and 10 mg/kg) or morphine (5 and 10 mg/kg) in the rat. A control group received normal saline. Sixty-three adult male Sprague-Dawley rats were anaesthetized with sevoflurane (n = 7 per group). Sevoflurane MAC was then determined before and after intraperitoneal administration of the opioids or saline. The duration of the sevoflurane MAC reduction and basic cardiovascular and respiratory measurements were also recorded. The baseline MAC was 2.5 (0.3) vol%. Methadone, tramadol and morphine reduced the sevoflurane MAC (low dose: 31 ± 10, 38 ± 15 and 30 ± 13% respectively; high dose: 100 ± 0, 83 ± 17 and 77 ± 25%, respectively) in a dose-dependent manner. The low and high doses of butorphanol reduced the sevoflurane MAC to a similar extent (33 ± 7 and 31 ± 4%, low and high doses, respectively). Two rats developed apnoea following administration of high-dose butorphanol and methadone. These anaesthetic-sparing effects are clinically relevant and may reduce the adverse effects associated with higher doses of inhalational anaesthetics.
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ketamine and remifentanil interactions on the sevoflurane Minimum Alveolar Concentration and acute opioid tolerance in the rat
Anesthesia & Analgesia, 2011Co-Authors: Delia Aguado, Javier Benito, Mariana Abreu, Javier Garciafernandez, Ignacio Gomez A De SeguraAbstract:Background Ketamine is used at low doses for its analgesic and antihyperalgesic properties when combined with opioids but also when opioid-induced hyperalgesia and tolerance appear. In this study we determined the interaction of ketamine and remifentanil on the Minimum Alveolar Concentration (MAC) of sevoflurane in rats and to determine whether ketamine may block acute opioid tolerance (AOT). Methods Male Wistar rats were anesthetized with sevoflurane, and the MAC was determined before and after ketamine administration (10, 20, 40, and 80 mg kg(-1) or saline) alone or combined with remifentanil (120 and 240 μg kg(-1) h(-1), low and high doses, respectively). One additional group received the lowest ketamine dose after starting a remifentanil infusion. Finally, naloxone was administered to determine the potential action of ketamine on opioid receptors. MAC was determined from intratracheal gas samples, and tail clamping was used as a supramaximal stimulus. End-tidal anesthetic Concentrations were assayed using a side stream gas analyzer. Statistical analysis was performed with an analysis of variance. Results Ketamine and remifentanil dose-dependently reduced the MAC. Adding the low dose of remifentanil to ketamine did not improve the MAC reduction, whereas the high dose of remifentanil enhanced ketamine reduction in a subadditive fashion. Nevertheless, ketamine was unable to block the development of AOT to remifentanil at either dose. Finally, naloxone blocked the MAC reduction produced by ketamine. Conclusions A subadditive effect between ketamine and remifentanil was found on the sevoflurane MAC reduction rats. In addition, ketamine was unable to block AOT. The clinical relevance of these findings should be elucidated in future studies to reduce anesthetic requirements.