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      Sedation with a remifentanil infusion to facilitate rapid awakening and tracheal extubation in an infant with a potentially compromised airway

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          Sedation is generally required during endotracheal intubation and mechanical ventilation in infants and children. While there are many options for the provision of sedation, the most commonly used agents such as midazolam and fentanyl demonstrate a context-sensitive half-life, which may result in a prolonged effect when these agents are discontinued following a continuous infusion. We present a 20-month-old infant who required endotracheal intubation due to respiratory failure following seizures. At the referring hospital, multiple laryngoscopies were performed with the potential for airway trauma. To maximize rapid awakening and optimize respiratory function surrounding tracheal extubation, sedation was transitioned from fentanyl and midazolam to remifentanil for 18–24 hours prior to tracheal extubation. The unique pharmacokinetics of remifentanil are presented in this study, its use in this clinical scenario is discussed, and its potential applications in the pediatric intensive care unit setting are reviewed.

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          Most cited references 24

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          Acute opioid tolerance: intraoperative remifentanil increases postoperative pain and morphine requirement.

          Rapid development of acute opioid tolerance is well established in animals and is more likely to occur with large doses of short-acting drugs. The authors therefore tested the hypothesis that intraoperative remifentanil administration results in acute opioid tolerance that is manifested by increased postoperative pain and opioid requirement. Fifty adult patients undergoing major abdominal surgery were randomly assigned to two anesthetic regimens: (1) desflurane was kept constant at 0.5 minimum alveolar concentrations and a remifentanil infusion was titrated to autonomic responses (remifentanil group); or (2) remifentanil at 0.1 microg. kg-1. min-1 and desflurane titrated to autonomic responses (desflurane group). All patients were given a bolus of 0.15 mg/kg morphine 40 min before the end of surgery. Morphine was initially titrated to need by postanesthesia care nurses blinded to group assignment. Subsequently, patients-who were also blinded to group assignment-controlled their own morphine administration. Pain scores and morphine consumption were recorded for 24 postoperative h. The mean remifentanil infusion rate was 0.3 +/- 0.2 microg. kg-1. min-1 in the remifentanil group, which was significantly greater than in the desflurane group. Intraoperative hemodynamic responses were similar in each group. Postoperative pain scores were significantly greater in the remifentanil group. These patients required morphine significantly earlier than those in the desflurane group and needed nearly twice as much morphine in the first 24 postoperative h: 59 mg (25-75% interquartile range, 43-71) versus 32 mg (25-75% interquartile range, 19-59; P < 0.01). Relatively large-dose intraoperative remifentanil increased postoperative pain and morphine consumption. These data suggest that remifentanil causes acute opioid tolerance and hyperalgesia.
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            Measured context-sensitive half-times of remifentanil and alfentanil.

            The context-sensitive half-time, rather than the terminal elimination half-life, has been proposed as a more clinically relevant measure of decreasing drug concentration after a constant infusion of a given duration. The context-sensitive half-time is derived from computer modelling using known pharmacokinetic parameters. The modelled context-sensitive half-time for a 3-h infusion of alfentanil is 50-55 min and is 3 min for remifentanil. The terminal elimination half-life is 111 min for alfentanil and 12-30 min for remifentanil. It has not been tested whether the modelled context-sensitive half-time reflects the true time for a 50% decrease in drug concentration or drug effect. Thirty volunteers received a 3-h infusion of remifentanil or alfentanil at equieffective concentrations. Depression of minute ventilation to 7.5% ETCO2 was used as a measure of drug effect. Minute ventilation response was measured, and blood samples for drug concentration were taken during and after drug infusion. The recovery of minute ventilation (drug effect) and decrease in blood drug concentration was plotted, and the time for a 50% change was determined. The measured pharmacokinetic context-sensitive half-time for remifentanil after a 3-h infusion was 3.2 +/- 0.9 min, and its pharmacodynamic offset was 5.4 +/- 1.8 min. Alfentanil's measured pharmacokinetic context-sensitive half-time was 47.3 +/- 12 min, and its pharmacodynamic offset was 54.0 +/- 48 min. The terminal elimination half-life modelled from the volunteers was 11.8 +/- 5.1 min for remifentanil and 76.5 +/- 12.6 min for alfentanil. The measured context-sensitive half-times were in close agreement with the context-sensitive half-times previously modelled for these drugs. The results of this study confirm the value of the context-sensitive half-time in describing drug offset compared to the terminal elimination half-life.
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              Rapid development of tolerance to analgesia during remifentanil infusion in humans.

               I Kissin,  H Vinik (1998)
              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.

                Author and article information

                J Pain Res
                J Pain Res
                Journal of Pain Research
                Journal of Pain Research
                Dove Medical Press
                27 October 2016
                : 9
                : 871-875
                [1 ]Department of Pediatrics, The Ohio State University
                [2 ]Division of Pediatric Critical Care Medicine, Nationwide Children’s Hospital
                [3 ]Department of Anesthesiology and Pain Medicine, Nationwide Children’s Hospital
                [4 ]Department of Anesthesiology and Pain Medicine, The Ohio State University, Columbus, OH, USA
                Author notes
                Correspondence: Jeffrey C Naples, Department of Pediatrics, Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH 43205, USA, Tel +1 614 722 3436, Email Jeffrey.Naples@ 123456nationwidechildrens.org
                © 2016 Naples et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Case Report

                Anesthesiology & Pain management

                extubation, airway, pediatric, sedation, remifentanil


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