An open label pilot study of a dexmedetomidine-remifentanil-caudal anesthetic for infant lower abdominal/lower extremity surgery: The T REX pilot study

Peter Szmuk, Dean Andropoulos, Francis McGowan, Ansgar Brambrink, Christopher Lee, Katherine J. Lee, Mary Ellen McCann, Yang Liu, Rita Saynhalath, Choon Looi Bong, Brian J. Anderson, Charles Berde, Jurgen C. De Graaff, Nicola Disma, Dean Kurth, Andreas Loepke, Beverley Orser, Daniel I. Sessler, Justin J. Skowno, Britta S. von Ungern-Sternberg & 2 others Laszlo Vutskits, Andrew Davidson

Research output: Contribution to journalArticle

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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 Results: One infant was excluded due to a protocol violation and consent was withdrawn prior to anesthesia in another.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.

Original languageEnglish
Pages (from-to)59-67
Number of pages9
JournalPaediatric Anaesthesia
Volume29
Issue number1
DOIs
Publication statusPublished - 1 Jan 2019

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Dexmedetomidine
Anesthetics
Lower Extremity
Anesthesia
Arterial Pressure
Hypotension
remifentanil
Poisons
Propofol
Local Anesthetics
Clinical Trials
Pharmacology
Hypertension

Cite this

Szmuk, Peter ; Andropoulos, Dean ; McGowan, Francis ; Brambrink, Ansgar ; Lee, Christopher ; Lee, Katherine J. ; McCann, Mary Ellen ; Liu, Yang ; Saynhalath, Rita ; Bong, Choon Looi ; Anderson, Brian J. ; Berde, Charles ; De Graaff, Jurgen C. ; Disma, Nicola ; Kurth, Dean ; Loepke, Andreas ; Orser, Beverley ; Sessler, Daniel I. ; Skowno, Justin J. ; von Ungern-Sternberg, Britta S. ; Vutskits, Laszlo ; Davidson, Andrew. / An open label pilot study of a dexmedetomidine-remifentanil-caudal anesthetic for infant lower abdominal/lower extremity surgery : The T REX pilot study. In: Paediatric Anaesthesia. 2019 ; Vol. 29, No. 1. pp. 59-67.
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title = "An open label pilot study of a dexmedetomidine-remifentanil-caudal anesthetic for infant lower abdominal/lower extremity surgery: The T REX pilot study",
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.",
keywords = "anesthesia caudal adverse effects, anesthesia general adverse effects, anesthesia general methods, brain/drug effects, dexmedetomidine, remifentanil",
author = "Peter Szmuk and Dean Andropoulos and Francis McGowan and Ansgar Brambrink and Christopher Lee and Lee, {Katherine J.} and McCann, {Mary Ellen} and Yang Liu and Rita Saynhalath and Bong, {Choon Looi} and Anderson, {Brian J.} and Charles Berde and {De Graaff}, {Jurgen C.} and Nicola Disma and Dean Kurth and Andreas Loepke and Beverley Orser and Sessler, {Daniel I.} and Skowno, {Justin J.} and {von Ungern-Sternberg}, {Britta S.} and Laszlo Vutskits and Andrew Davidson",
year = "2019",
month = "1",
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doi = "10.1111/pan.13544",
language = "English",
volume = "29",
pages = "59--67",
journal = "Pediatric Anesthesia",
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Szmuk, P, Andropoulos, D, McGowan, F, Brambrink, A, Lee, C, Lee, KJ, McCann, ME, Liu, Y, Saynhalath, R, Bong, CL, Anderson, BJ, Berde, C, De Graaff, JC, Disma, N, Kurth, D, Loepke, A, Orser, B, Sessler, DI, Skowno, JJ, von Ungern-Sternberg, BS, Vutskits, L & Davidson, A 2019, 'An open label pilot study of a dexmedetomidine-remifentanil-caudal anesthetic for infant lower abdominal/lower extremity surgery: The T REX pilot study' Paediatric Anaesthesia, vol. 29, no. 1, pp. 59-67. https://doi.org/10.1111/pan.13544

An open label pilot study of a dexmedetomidine-remifentanil-caudal anesthetic for infant lower abdominal/lower extremity surgery : The T REX pilot study. / Szmuk, Peter; Andropoulos, Dean; McGowan, Francis; Brambrink, Ansgar; Lee, Christopher; Lee, Katherine J.; McCann, Mary Ellen; Liu, Yang; Saynhalath, Rita; Bong, Choon Looi; Anderson, Brian J.; Berde, Charles; De Graaff, Jurgen C.; Disma, Nicola; Kurth, Dean; Loepke, Andreas; Orser, Beverley; Sessler, Daniel I.; Skowno, Justin J.; von Ungern-Sternberg, Britta S.; Vutskits, Laszlo; Davidson, Andrew.

In: Paediatric Anaesthesia, Vol. 29, No. 1, 01.01.2019, p. 59-67.

Research output: Contribution to journalArticle

TY - JOUR

T1 - An open label pilot study of a dexmedetomidine-remifentanil-caudal anesthetic for infant lower abdominal/lower extremity surgery

T2 - The T REX pilot study

AU - Szmuk, Peter

AU - Andropoulos, Dean

AU - McGowan, Francis

AU - Brambrink, Ansgar

AU - Lee, Christopher

AU - Lee, Katherine J.

AU - McCann, Mary Ellen

AU - Liu, Yang

AU - Saynhalath, Rita

AU - Bong, Choon Looi

AU - Anderson, Brian J.

AU - Berde, Charles

AU - De Graaff, Jurgen C.

AU - Disma, Nicola

AU - Kurth, Dean

AU - Loepke, Andreas

AU - Orser, Beverley

AU - Sessler, Daniel I.

AU - Skowno, Justin J.

AU - von Ungern-Sternberg, Britta S.

AU - Vutskits, Laszlo

AU - Davidson, Andrew

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - anesthesia caudal adverse effects

KW - anesthesia general adverse effects

KW - anesthesia general methods

KW - brain/drug effects

KW - dexmedetomidine

KW - remifentanil

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DO - 10.1111/pan.13544

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JO - Pediatric Anesthesia

JF - Pediatric Anesthesia

SN - 1155-5645

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