Peter Szmuk1,2, Dean Andropoulos3, Francis McGowan4, Ansgar Brambrink5, Christopher Lee6, Katherine J Lee7, Mary Ellen McCann8, Yang Liu3, Rita Saynhalath1, Choon Looi Bong9, Brian J Anderson10, Charles Berde8, Jurgen C De Graaff11, Nicola Disma12,13, Dean Kurth4, Andreas Loepke4, Beverley Orser14, Daniel I Sessler2, Justin J Skowno15, Britta S von Ungern-Sternberg16, Laszlo Vutskits17, Andrew Davidson18. 1. Department of Anesthesiology and Pain Management, University of Texas Southwestern and Children's Medical Centre Dallas, Dallas, Texas. 2. Department of Outcomes Research, Cleveland Clinic, Cleveland, Ohio. 3. Department of Anesthesiology, Texas Children's Hospital, Houston, Texas. 4. Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. 5. Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, Oregon. 6. Department of Anesthesiology, Cincinnati Children's Hospital Medical Centre, Cincinnati, Ohio. 7. Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, the University of Melbourne, Parkville, Victoria, Australia. 8. Department of Anesthesiology, Pain and Perioperative Medicine, Boston Children's Hospital, Boston, Massachusetts. 9. Department of Paediatric Anaesthesia, KK Women's and Children's Hospital, Singapore, Singapore. 10. Department of Anaesthesiology, University of Auckland and Auckland Children's Hospital, Auckland, New Zealand. 11. Department of Anesthesia, ErasmusMC-Sophia Children's Hospital, Rotterdam, The Netherlands. 12. Department of Anesthesia, Gaslini Children's Hospital, Genoa, Italy. 13. Department of Anesthesia, Greast Osmond Street Hospital for Children, NHS Foundation Trust, London, UK. 14. Department of Anesthesia, University of Toronto, Toronto, ON, Canada. 15. Department of Anaesthesia, The Children's Hospital at Westmead, Sydney, New South Wales, Australia. 16. Department of Anaesthesia and Pain Medicine, Perth Children's Hospital, The University of Western Australia Medical School, Perth, Western Australia, Australia. 17. Department of Anesthesiology, Pharmacology, and Intensive Care, University Hospitals of Geneva, Geneva, Switzerland. 18. Department of Anaesthesia, Royal Children's Hospital, Parkville, Victoria, Australia.
Abstract
BACKGROUND: Concern over potential neurotoxicity of anesthetics has led to growing interest in prospective clinical trials using potentially less toxic anesthetic regimens, especially for prolonged anesthesia in infants. Preclinical studies suggest that dexmedetomidine may have a reduced neurotoxic profile compared to other conventional anesthetic regimens; however, coadministration with either anesthetic drugs (eg, remifentanil) and/or regional blockade is required to achieve adequate anesthesia for surgery. The feasibility of this pharmacological approach is unknown. The aim of this study was to determine the feasibility of a remifentanil/dexmedetomidine/neuraxial block technique in infants scheduled for surgery lasting longer than 2 hours. METHODS: Sixty infants (age 1-12 months) were enrolled at seven centers over 18 months. A caudal local anesthetic block was placed after induction of anesthesia with sevoflurane. Next, an infusion of dexmedetomidine and remifentanil commenced, and the sevoflurane was discontinued. Three different protocols with escalating doses of dexmedetomidine and remifentanil were used. RESULTS: One infant was excluded due to a protocol violation and consent was withdrawn prior to anesthesia in another. The caudal block was unsuccessful in two infants. Of the 56 infants who completed the protocol, 45 (80%) had at least one episode of hypertension (mean arterial pressure >80 mm Hg) and/or movement that required adjusting the anesthesia regimen. In the majority of these cases, the remifentanil and/or dexmedetomidine doses were increased although six infants required rescue 0.3% sevoflurane and one required a propofol bolus. Ten infants had at least one episode of mild hypotension (mean arterial pressure 40-50 mm Hg) and four had at least one episode of moderate hypotension (mean arterial pressure <40 mm Hg). CONCLUSION: A dexmedetomidine/remifentanil neuraxial anesthetic regimen was effective in 87.5% of infants. These findings can be used as a foundation for designing larger trials that assess alternative anesthetic regimens for anesthetic neurotoxicity in infants.
BACKGROUND: Concern over potential neurotoxicity of anesthetics has led to growing interest in prospective clinical trials using potentially less toxic anesthetic regimens, especially for prolonged anesthesia in infants. Preclinical studies suggest that dexmedetomidine may have a reduced neurotoxic profile compared to other conventional anesthetic regimens; however, coadministration with either anesthetic drugs (eg, remifentanil) and/or regional blockade is required to achieve adequate anesthesia for surgery. The feasibility of this pharmacological approach is unknown. The aim of this study was to determine the feasibility of a remifentanil/dexmedetomidine/neuraxial block technique in infants scheduled for surgery lasting longer than 2 hours. METHODS: Sixty infants (age 1-12 months) were enrolled at seven centers over 18 months. A caudal local anesthetic block was placed after induction of anesthesia with sevoflurane. Next, an infusion of dexmedetomidine and remifentanil commenced, and the sevoflurane was discontinued. Three different protocols with escalating doses of dexmedetomidine and remifentanil were used. RESULTS: One infant was excluded due to a protocol violation and consent was withdrawn prior to anesthesia in another. The caudal block was unsuccessful in two infants. Of the 56 infants who completed the protocol, 45 (80%) had at least one episode of hypertension (mean arterial pressure >80 mm Hg) and/or movement that required adjusting the anesthesia regimen. In the majority of these cases, the remifentanil and/or dexmedetomidine doses were increased although six infants required rescue 0.3% sevoflurane and one required a propofol bolus. Ten infants had at least one episode of mild hypotension (mean arterial pressure 40-50 mm Hg) and four had at least one episode of moderate hypotension (mean arterial pressure <40 mm Hg). CONCLUSION: A dexmedetomidine/remifentanil neuraxial anesthetic regimen was effective in 87.5% of infants. These findings can be used as a foundation for designing larger trials that assess alternative anesthetic regimens for anesthetic neurotoxicity in infants.
Authors: Kristin Keunen; Nicolaas H Sperna Weiland; Bernadette S de Bakker; Linda S de Vries; Markus F Stevens Journal: Paediatr Anaesth Date: 2022-03-16 Impact factor: 2.129
Authors: Camille E van Hoorn; Robert B Flint; Justin Skowno; Paul Davies; Thomas Engelhardt; Kirk Lalwani; Olutoyin Olutoye; Erwin Ista; Jurgen C de Graaff Journal: Eur J Clin Pharmacol Date: 2020-10-29 Impact factor: 2.953