Clinical Trial

. 2024 Dec 1;141(6):1075-1085.

doi: 10.1097/ALN.0000000000005232.

Short-term Outcomes in Infants after General Anesthesia with Low-dose Sevoflurane/Dexmedetomidine/Remifentanil versus Standard-dose Sevoflurane (the TREX Trial)

Rita Saynhalath¹, Nicola Disma², Fiona J Taverner³, Britta S von Ungern-Sternberg⁴, Dean Andropoulos⁵, Ann S Ng⁵, Benjamin B Shields⁵, Francesca Izzo⁶, Paul Lee-Archer⁷, Mary Ellen McCann⁸, Luigi Montagnini⁹, Beate Kuppers¹⁰, Elena Lenares¹¹, Suzette Sheppard¹², Jurgen C de Graaff¹³, Katherine J Lee¹⁴, Xiaofang Wang¹⁵, Peter Szmuk¹⁶, Andrew J Davidson¹⁷, Justin J Skowno¹⁸; TREX (Trial Remifentanil DEXmedetomidine) Consortium

Collaborators, Affiliations

Collaborators

TREX (Trial Remifentanil DEXmedetomidine) Consortium:
Andrew Davidson¹⁹, Nicola Disma²⁰, Francesca Izzo²¹, Luigi Montagnini²², Elena Lenares²³, Beate Kuppers²⁴, Sergio Picardo, Isabella Tucci, Alessandra Di Persio²⁵, Simona Neri²⁶, Fabio Caramelli²⁷, Peter Szmuk²⁸, Dean Andropoulos, Eduardo Medellin²⁹, Mary Ellen McCann³⁰, Christopher Ward³¹, Pilar Castro³², Paul Lee-Archer³³, Justin Skowno³⁴, Britta von Ungern Sternberg³⁵, Fiona Taverner³⁶, Fiona Taverner³⁷, Shona Chung³⁸, Andrew Davidson, Suzette Sheppard, Louise Crowe

Affiliations

¹ Department of Anesthesiology and Pain Management, University of Texas Southwestern and Children's Health, Dallas, Texas; and Department of Outcomes Research, Cleveland Clinic, Cleveland, Ohio.
² Unit for Research in Anaesthesia, IRCCS Istituto Giannina Gaslini, Genova, Italy.
³ Flinders University, College of Medicine and Public Health, Adelaide, South Australia, Australia; Department of Anaesthesia and Pain Medicine, Flinders Medical Centre, Adelaide, South Australia, Australia; and Department of Children's Anaesthesia, Women's and Children's Hospital, North Adelaide, South Australia, Australia.
⁴ Department of Anaesthesia and Pain Medicine, Perth Children's Hospital, Perth, Western Australia, Australia; Division of Emergency Medicine, Anaesthesia and Pain Medicine, Medical School, University of Western Australia, Perth, Western Australia, Australia; Institute for Paediatric Perioperative Excellence, University of Western Australia, Perth, Western Australia, Australia; and Perioperative Medicine Team, Perioperative Care Program, Telethon Kids Institute, Perth, Western Australia, Australia.
⁵ Department of Anesthesiology, Texas Children's Hospital and Baylor College of Medicine, Houston, Texas.
⁶ Department of Pediatric Anesthesia and Intensive Care, Children's Hospital "Vittore Buzzi," Milan, Italy.
⁷ Department of Anaesthesia, Queensland Children's Hospital, Faculty of Medicine, University of Queensland, South Brisbane, Queensland, Australia.
⁸ Department of Anesthesiology, Pain and Perioperative Medicine, Boston Children's Hospital, Boston, Massachusetts.
⁹ Unit of Anesthesia and Critical Care, Department of Emergency, Grande Ospedale Metropolitano Niguarda, Milano, Italy; and Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo, Alessandria, Italy.
¹⁰ Department of Anesthesia and Intensive Care, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
¹¹ University Hospital (AOU) Meyer, Florence, Italy.
¹² Department of Anaesthesia, The Royal Children's Hospital, Victoria, Australia; and Anaesthesia Research Group, Murdoch Children's Research Institute, Victoria, Australia.
¹³ Department of Anesthesiology, Admiraal de Ruyter Hospital-Erasmus Medical Center, Goes, The Netherlands; and Department of Anesthesiology, Weill Cornell Medicine, New York, New York.
¹⁴ Clinical Epidemiology and Biostatistics Unit and Melbourne Children's Trials Centre, Murdoch Children's Research Institute, Victoria, Australia; and Department of Paediatrics, University of Melbourne, Victoria, Australia.
¹⁵ Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Victoria, Australia.
¹⁶ Department of Outcomes Research, Cleveland Clinic, Cleveland, Ohio; and Department of Anesthesiology and Pain Management, University of Texas Southwestern and Children's Health, Dallas, Texas.
¹⁷ Department of Anaesthesia, The Royal Children's Hospital, Victoria, Australia; Department of Paediatrics, University of Melbourne, Victoria, Australia; and Anaesthesia Research Group, Murdoch Children's Research Institute, Victoria, Australia.
¹⁸ The Children's Hospital at Westmead, Sydney, New South Wales, Australia; and University of Sydney, Sydney, New South Wales, Australia.
¹⁹ IRCCS Istituto Giannina Gaslini, Genova, Italy.
²⁰ Ospedale dei Bambini "Vittore Buzzi," Milano, Italy.
²¹ Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo, Alessandria, Italy.
²² IRCCS Azienda Ospedaliero-Universitaria Meyer, Firenze, Italy.
²³ Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
²⁴ IRCCS Ospedale Pediatrico Bambino Gesù, Roma, Italy.
²⁵ IRCCS Ca' Granda Ospedale Maggiore Policlinico-Clinica Mangiagalli, Milano, Italy.
²⁶ Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi, Bologna, Italy.
²⁷ Children's Health, Dallas, Texas.
²⁸ Texas Children's Hospital, Houston, Texas.
²⁹ Boston Children's Hospital, Boston, Massachusetts.
³⁰ Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
³¹ Cleveland Clinic, Cleveland, Ohio.
³² Queensland Children's Hospital, Australia.
³³ The Children's Hospital Westmead, Sydney, New South Wales, Australia.
³⁴ Perth Children's Hospital, Perth, Western Australia, Australia.
³⁵ Flinders Medical Center, Bedford Park, South Australia, Australia.
³⁶ Women and Children's Hospital Adelaide, Adelaide, South Australia, Australia.
³⁷ Sydney Children's Hospital, Sydney, New South Wales, Australia.
³⁸ The Royal Children's Hospital Melbourne, Melbourne, Victoria, Australia.

PMID: 39283983
DOI: 10.1097/ALN.0000000000005232

Clinical Trial

Short-term Outcomes in Infants after General Anesthesia with Low-dose Sevoflurane/Dexmedetomidine/Remifentanil versus Standard-dose Sevoflurane (the TREX Trial)

Rita Saynhalath et al. Anesthesiology. 2024.

. 2024 Dec 1;141(6):1075-1085.

doi: 10.1097/ALN.0000000000005232.

Authors

Collaborators

TREX (Trial Remifentanil DEXmedetomidine) Consortium:
Andrew Davidson¹⁹, Nicola Disma²⁰, Francesca Izzo²¹, Luigi Montagnini²², Elena Lenares²³, Beate Kuppers²⁴, Sergio Picardo, Isabella Tucci, Alessandra Di Persio²⁵, Simona Neri²⁶, Fabio Caramelli²⁷, Peter Szmuk²⁸, Dean Andropoulos, Eduardo Medellin²⁹, Mary Ellen McCann³⁰, Christopher Ward³¹, Pilar Castro³², Paul Lee-Archer³³, Justin Skowno³⁴, Britta von Ungern Sternberg³⁵, Fiona Taverner³⁶, Fiona Taverner³⁷, Shona Chung³⁸, Andrew Davidson, Suzette Sheppard, Louise Crowe

Affiliations

¹ Department of Anesthesiology and Pain Management, University of Texas Southwestern and Children's Health, Dallas, Texas; and Department of Outcomes Research, Cleveland Clinic, Cleveland, Ohio.
² Unit for Research in Anaesthesia, IRCCS Istituto Giannina Gaslini, Genova, Italy.
³ Flinders University, College of Medicine and Public Health, Adelaide, South Australia, Australia; Department of Anaesthesia and Pain Medicine, Flinders Medical Centre, Adelaide, South Australia, Australia; and Department of Children's Anaesthesia, Women's and Children's Hospital, North Adelaide, South Australia, Australia.
⁴ Department of Anaesthesia and Pain Medicine, Perth Children's Hospital, Perth, Western Australia, Australia; Division of Emergency Medicine, Anaesthesia and Pain Medicine, Medical School, University of Western Australia, Perth, Western Australia, Australia; Institute for Paediatric Perioperative Excellence, University of Western Australia, Perth, Western Australia, Australia; and Perioperative Medicine Team, Perioperative Care Program, Telethon Kids Institute, Perth, Western Australia, Australia.
⁵ Department of Anesthesiology, Texas Children's Hospital and Baylor College of Medicine, Houston, Texas.
⁶ Department of Pediatric Anesthesia and Intensive Care, Children's Hospital "Vittore Buzzi," Milan, Italy.
⁷ Department of Anaesthesia, Queensland Children's Hospital, Faculty of Medicine, University of Queensland, South Brisbane, Queensland, Australia.
⁸ Department of Anesthesiology, Pain and Perioperative Medicine, Boston Children's Hospital, Boston, Massachusetts.
⁹ Unit of Anesthesia and Critical Care, Department of Emergency, Grande Ospedale Metropolitano Niguarda, Milano, Italy; and Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo, Alessandria, Italy.
¹⁰ Department of Anesthesia and Intensive Care, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
¹¹ University Hospital (AOU) Meyer, Florence, Italy.
¹² Department of Anaesthesia, The Royal Children's Hospital, Victoria, Australia; and Anaesthesia Research Group, Murdoch Children's Research Institute, Victoria, Australia.
¹³ Department of Anesthesiology, Admiraal de Ruyter Hospital-Erasmus Medical Center, Goes, The Netherlands; and Department of Anesthesiology, Weill Cornell Medicine, New York, New York.
¹⁴ Clinical Epidemiology and Biostatistics Unit and Melbourne Children's Trials Centre, Murdoch Children's Research Institute, Victoria, Australia; and Department of Paediatrics, University of Melbourne, Victoria, Australia.
¹⁵ Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Victoria, Australia.
¹⁶ Department of Outcomes Research, Cleveland Clinic, Cleveland, Ohio; and Department of Anesthesiology and Pain Management, University of Texas Southwestern and Children's Health, Dallas, Texas.
¹⁷ Department of Anaesthesia, The Royal Children's Hospital, Victoria, Australia; Department of Paediatrics, University of Melbourne, Victoria, Australia; and Anaesthesia Research Group, Murdoch Children's Research Institute, Victoria, Australia.
¹⁸ The Children's Hospital at Westmead, Sydney, New South Wales, Australia; and University of Sydney, Sydney, New South Wales, Australia.
¹⁹ IRCCS Istituto Giannina Gaslini, Genova, Italy.
²⁰ Ospedale dei Bambini "Vittore Buzzi," Milano, Italy.
²¹ Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo, Alessandria, Italy.
²² IRCCS Azienda Ospedaliero-Universitaria Meyer, Firenze, Italy.
²³ Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
²⁴ IRCCS Ospedale Pediatrico Bambino Gesù, Roma, Italy.
²⁵ IRCCS Ca' Granda Ospedale Maggiore Policlinico-Clinica Mangiagalli, Milano, Italy.
²⁶ Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi, Bologna, Italy.
²⁷ Children's Health, Dallas, Texas.
²⁸ Texas Children's Hospital, Houston, Texas.
²⁹ Boston Children's Hospital, Boston, Massachusetts.
³⁰ Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
³¹ Cleveland Clinic, Cleveland, Ohio.
³² Queensland Children's Hospital, Australia.
³³ The Children's Hospital Westmead, Sydney, New South Wales, Australia.
³⁴ Perth Children's Hospital, Perth, Western Australia, Australia.
³⁵ Flinders Medical Center, Bedford Park, South Australia, Australia.
³⁶ Women and Children's Hospital Adelaide, Adelaide, South Australia, Australia.
³⁷ Sydney Children's Hospital, Sydney, New South Wales, Australia.
³⁸ The Royal Children's Hospital Melbourne, Melbourne, Victoria, Australia.

PMID: 39283983
DOI: 10.1097/ALN.0000000000005232

Abstract

Background: The Trial Remifentanil DEXmedetomidine (TREX) trial aimed to determine whether, in children less than 2 yr old, low-dose sevoflurane/dexmedetomidine/remifentanil anesthesia is superior to standard-dose sevoflurane anesthesia in terms of global cognitive function at 3 yr of age. The aim of the current secondary analyses was to compare incidence of intraoperative hypotension and bradycardia, postoperative pain, time to recovery, need for treatment of intraoperative hypotension and bradycardia, incidence of light anesthesia and need for treatment, need for postoperative pain medications, and morbidity and mortality outcomes at 5 days between the two arms.

Methods: This phase III randomized active controlled, parallel group, assessor blinded, multicenter, superiority trial was performed in 20 centers in Australia, Italy, and the United States. A total of 455 infants less than 2 yr of age expected to undergo general anesthesia for at least 2 h were enrolled. They were randomized between low-dose sevoflurane/dexmedetomidine/remifentanil anesthesia and standard-dose sevoflurane. The short-term perioperative outcomes noted above were compared between these two groups.

Results: There was less hypotension (risk difference, -11.6%; 95% CI, -18.9 to -4.3%) and more bradycardia (risk difference, 18.2%; 95% CI, 8.8 to 27.7%) in the low-dose sevoflurane/dexmedetomidine/remifentanil anesthesia compared to the standard-dose sevoflurane arm. There were more patients with episodes of light anesthesia (89 vs. 4), and protocol abandonments (1 vs. 0) in the low-dose sevoflurane/dexmedetomidine/remifentanil anesthesia arm. Time from eye opening to postanesthesia care unit discharge was similar in both arms, as were morbidity and mortality. One patient in each arm suffered a life-threatening event, but neither suffered long-term sequelae.

Conclusions: These early postoperative results suggest that in children less than 2 yr of age receiving greater than 2 h of general anesthesia, the low-dose sevoflurane/dexmedetomidine/remifentanil anesthesia technique and the standard sevoflurane anesthesia technique are broadly clinically similar, with no clear evidence to support choosing one technique over the other.

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References

1. Rappaport BA, Suresh S, Hertz S, Evers AS, Orser BA: Anesthetic neurotoxicity—Clinical implications of animal models. N Engl J Med 2015; 372:796–7
1. FDA Drug Safety Communication: FDA review results in new warnings about using general anaesthetics and sedation drugs in young children and pregnant women. December 14, 2016. Available at: https://www.fda.gov/media/101937/download . Accessed November 30, 2023.
1. FDA Drug Safety Communication: FDA approves label changes for use of general anaesthetic and sedation drugs in young children. April 27, 2017. Available at: https://www.fda.gov/media/104705/download . Accessed November 30, 2023.
1. McCann ME, de Graaff JC, Dorris L, et al.; GAS Consortium: Neurodevelopmental outcome at 5 years of age after general anaesthesia or awake-regional anaesthesia in infancy (GAS): An international, multicentre, randomised, controlled equivalence trial. Lancet 2019; 393:664–77
1. Ing C, Warner DO, Sun LS, et al.: Anesthesia and developing brains: Unanswered questions and proposed paths forward. A nesthesiology 2022; 136:500–12

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Short-term Outcomes in Infants after General Anesthesia with Low-dose Sevoflurane/Dexmedetomidine/Remifentanil versus Standard-dose Sevoflurane (the TREX Trial)

Collaborators

Affiliations

Short-term Outcomes in Infants after General Anesthesia with Low-dose Sevoflurane/Dexmedetomidine/Remifentanil versus Standard-dose Sevoflurane (the TREX Trial)

Authors

Collaborators

Affiliations

Abstract

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources