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

Rita Saynhalath; Nicola Disma; Fiona J Taverner; Britta S von Ungern-Sternberg; Dean Andropoulos; Ann S Ng; Benjamin B Shields; Francesca Izzo; Paul Lee-Archer; Mary Ellen McCann; Luigi Montagnini; Beate Kuppers; Elena Lenares; Suzette Sheppard; Jurgen C de Graaff; Katherine J Lee; Xiaofang Wang; Peter Szmuk; Andrew J Davidson; Justin J Skowno; TREX (Trial Remifentanil DEXmedetomidine) Consortium

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)

Anesthesiology. 2024 Dec 1;141(6):1075-1085. doi: 10.1097/ALN.0000000000005232.

Authors

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

TREX (Trial Remifentanil DEXmedetomidine) Consortium:
Andrew Davidson, Nicola Disma, Francesca Izzo, Luigi Montagnini, Elena Lenares, Beate Kuppers, Sergio Picardo, Isabella Tucci, Alessandra Di Persio, Simona Neri, Fabio Caramelli, Peter Szmuk, Dean Andropoulos, Eduardo Medellin, Mary Ellen McCann, Christopher Ward, Pilar Castro, Paul Lee-Archer, Justin Skowno, Britta von Ungern Sternberg, Fiona Taverner, Fiona Taverner, Shona Chung, 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.

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.

Publication types

Randomized Controlled Trial
Multicenter Study
Comparative Study
Clinical Trial, Phase III

MeSH terms

Anesthesia, General* / methods
Anesthetics, Combined / administration & dosage
Anesthetics, Inhalation* / administration & dosage
Bradycardia / chemically induced
Bradycardia / epidemiology
Dexmedetomidine* / administration & dosage
Dexmedetomidine* / adverse effects
Dose-Response Relationship, Drug
Female
Humans
Infant
Male
Methyl Ethers / administration & dosage
Remifentanil* / administration & dosage
Remifentanil* / adverse effects
Sevoflurane* / administration & dosage
Treatment Outcome

Substances

Sevoflurane
Remifentanil
Dexmedetomidine
Anesthetics, Inhalation
Methyl Ethers
Anesthetics, Combined