{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:52:56Z","timestamp":1747187576321,"version":"3.40.5"},"reference-count":26,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,9,25]],"date-time":"2022-09-25T00:00:00Z","timestamp":1664064000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Anesthesia"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>A single caudal anesthetic at the start of lower abdominal surgery is unlikely to provide prolonged analgesia. A second caudal at the end of the procedure extends the analgesia duration but total plasma concentrations may be associated with toxicity. Our aim was to measure total plasma levobupivacaine concentrations after repeat caudal anesthesia in infants and to generate a pharmacokinetic model for prediction of plasma concentrations after repeat caudal anesthesia in neonates, infants and children.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Infants undergoing definitive repair of anorectal malformations or Hirschsprung's disease received a second caudal anesthesia at the end of the procedure. Total levobupivacaine concentrations were assayed 3\u20134 times in the first 6\u00a0h after the initial caudal. These data were pooled with data from four studies describing plasma concentrations after levobupivacaine caudal or spinal anesthesia. Population pharmacokinetic parameters were estimated using nonlinear mixed\u2010effects models. Covariates included postmenstrual age and body weight. Parameter estimates were used to simulate concentrations after a repeat levobupivacaine 2.5\u00a0mg\u2009kg<jats:sup>\u22121<\/jats:sup> caudal at 3 or 4\u00a0h following an initial levobupivacaine 2.5\u00a0mg\u2009kg<jats:sup>\u22121<\/jats:sup> caudal.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty\u2010one infants (postnatal age 11\u201332\u2009weeks, gestation 37\u201339\u2009weeks, weight 5.2\u20138.6\u00a0kg) were included. The measured peak plasma concentration after repeat caudal levobupivacaine 2.5\u00a0mg\u2009kg<jats:sup>\u22121<\/jats:sup> 4\u2009h after initial caudal was 1.38\u2009mg\u2009L<jats:sup>\u22121<\/jats:sup> (95% prediction interval 0.60\u20132.6\u00a0mg\u2009L<jats:sup>\u22121<\/jats:sup>) and 3\u2009h after initial caudal was 1.46\u2009mg\u2009L<jats:sup>\u22121<\/jats:sup> (0.60\u20132.80)\u00a0mg\u2009L<jats:sup>\u22121<\/jats:sup>. Simulation of total plasma concentrations in neonates (7\u00a0kg, 57\u2009weeks postmenstrual age) given caudal levobupivacaine 4\u2009h after the initial caudal were 1.76\u2009mg\u2009L<jats:sup>\u22121<\/jats:sup> (0.68\u20133.50) mg\u2009L<jats:sup>\u22121<\/jats:sup> if 2.5\u00a0mg\u2009kg<jats:sup>\u22121<\/jats:sup> levobupivacaine was used and 0.88\u2009mg\u2009L<jats:sup>\u22121<\/jats:sup> (0.34\u20131.73)\u00a0mg\u2009L<jats:sup>\u22121<\/jats:sup> if 1.25\u2009mg\u2009kg<jats:sup>\u22121<\/jats:sup> of 0.125% levobupivacaine was used. In simulated older children (20\u2009kg, 6\u2009years), the mean maximum concentration was 1.43\u2009mg\u2009L<jats:sup>\u22121<\/jats:sup> (0.60\u20132.70)\u00a0mg\u2009L<jats:sup>\u22121<\/jats:sup> if 2.5\u00a0mg\u2009kg<jats:sup>\u22121<\/jats:sup> levobupivacaine was repeated at 3\u00a0h.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Repeat caudal levobupivacaine 2.5\u00a0mg\u2009kg<jats:sup>\u22121<\/jats:sup> at 3\u00a0h after an initial 2.5\u00a0mg\u2009kg<jats:sup>\u22121<\/jats:sup> dose does not exceed the concentration associated with systemic local anesthetic toxicity. In 2.5% of simulated neonates (weight 3.8\u00a0kg, PMA 40\u2009weeks), repeat caudal anesthesia demonstrates broaching of the lower concentration limit associated with toxicity at both 3 and 4\u2009h after initial caudal.<\/jats:p><\/jats:sec>","DOI":"10.1111\/pan.14556","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T06:48:12Z","timestamp":1663224492000},"page":"1347-1354","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Levobupivacaine plasma concentrations following repeat caudal anesthetics"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4225-1185","authenticated-orcid":false,"given":"Geoff","family":"Frawley","sequence":"first","affiliation":[{"name":"Department of Paediatric Anaesthesia and Pain Management Royal Children's Hospital Melbourne  Parkville Victoria Australia"},{"name":"Department of Paediatrics University of Melbourne  Parkville Victoria Australia"},{"name":"Critical Care and Neurosciences Theme Murdoch Children's Research Institute  Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8544-8768","authenticated-orcid":false,"given":"Luis Ignacio","family":"Cortinez","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n Anestesiolog\u00eda, Escuela de Medicina Pontificia Universidad Cat\u00f3lica de Chile  Santiago de Chile Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2826-3019","authenticated-orcid":false,"given":"Brian J.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology University of Auckland  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Bjorksten","sequence":"additional","affiliation":[{"name":"Department Anaesthesia and Pain Management Royal Melbourne 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