Anesthesia and the developing brain: A way forward for laboratory and clinical research

Nicola Disma*, James D. O'Leary, Andreas W. Loepke, Ansgar M. Brambrink, Karin Becke, Nicola G. Clausen, Jurgen C. De Graaff, Fang Liu, Tom G. Hansen, Mary E. McCann, Cynthia F. Salorio, Sulpicio Soriano, Lena S. Sun, Peter Szmuk, David O. Warner, Laszlo Vutskits, Andrew J. Davidson

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftReviewForskningpeer review

Resumé

All commonly used general anesthetics have been shown to cause neurotoxicity in animal models, including nonhuman primates. Opinion, however, remains divided over how cumulative evidence from preclinical and human studies in this field should be interpreted and its translation to current practices in pediatric anesthesia and surgery. A group of international experts in laboratory and clinical sciences recently convened in Genoa, Italy, to evaluate the current state of both laboratory and clinical research and discuss future directions for basic, translational, and clinical studies in this field. This paper describes those discussions and conclusions. A central goal identified was the importance of continuing to pursue laboratory research efforts to better understand the biological pathways underlying anesthesia neurotoxicity. The distinction between basic and translational experimental designs in this field was highlighted, and it was acknowledged that it will be important for future animal research to try to causally link structural changes with long-term cognitive abnormalities. While inherent limitations will continue to affect the ability of even large observational cohorts to determine if anesthesia impacts neurodevelopment or behavioral outcomes, the importance of conducting further large well-designed cohort studies was also emphasized. Adequately powered cohorts could clarify which populations are at increased risk, provide information on environmental and healthcare-related risk modifiers, and guide future interventional trials. If anesthetics cause structural or functional adverse neurological effects in young children, alternative or mitigating strategies need to be considered. While protective or mitigating strategies have been repeatedly studied in animals, there are currently no human data to support alternative anesthetic strategies in clinical practice. Lastly, it was noted that there is still considerable debate over the clinical relevance of anesthesia neurotoxicity, and the need to evaluate the impact of other aspects of perioperative care on neurodevelopment must also be considered.

OriginalsprogEngelsk
TidsskriftPaediatric Anaesthesia
Vol/bind28
Udgave nummer9
Sider (fra-til)758-763
ISSN1155-5645
DOI
StatusUdgivet - 1. sep. 2018

Fingeraftryk

Research
Primates
Italy
Cohort Studies
Research Design
Pediatrics
Delivery of Health Care
Clinical Studies
Direction compound

Bibliografisk note

© 2018 John Wiley & Sons Ltd.

Citer dette

Disma, N., O'Leary, J. D., Loepke, A. W., Brambrink, A. M., Becke, K., Clausen, N. G., ... Davidson, A. J. (2018). Anesthesia and the developing brain: A way forward for laboratory and clinical research. Paediatric Anaesthesia, 28(9), 758-763. https://doi.org/10.1111/pan.13455
Disma, Nicola ; O'Leary, James D. ; Loepke, Andreas W. ; Brambrink, Ansgar M. ; Becke, Karin ; Clausen, Nicola G. ; De Graaff, Jurgen C. ; Liu, Fang ; Hansen, Tom G. ; McCann, Mary E. ; Salorio, Cynthia F. ; Soriano, Sulpicio ; Sun, Lena S. ; Szmuk, Peter ; Warner, David O. ; Vutskits, Laszlo ; Davidson, Andrew J. / Anesthesia and the developing brain : A way forward for laboratory and clinical research. I: Paediatric Anaesthesia. 2018 ; Bind 28, Nr. 9. s. 758-763.
@article{81b7512ce2d04c45808ae05cd1acec88,
title = "Anesthesia and the developing brain: A way forward for laboratory and clinical research",
abstract = "All commonly used general anesthetics have been shown to cause neurotoxicity in animal models, including nonhuman primates. Opinion, however, remains divided over how cumulative evidence from preclinical and human studies in this field should be interpreted and its translation to current practices in pediatric anesthesia and surgery. A group of international experts in laboratory and clinical sciences recently convened in Genoa, Italy, to evaluate the current state of both laboratory and clinical research and discuss future directions for basic, translational, and clinical studies in this field. This paper describes those discussions and conclusions. A central goal identified was the importance of continuing to pursue laboratory research efforts to better understand the biological pathways underlying anesthesia neurotoxicity. The distinction between basic and translational experimental designs in this field was highlighted, and it was acknowledged that it will be important for future animal research to try to causally link structural changes with long-term cognitive abnormalities. While inherent limitations will continue to affect the ability of even large observational cohorts to determine if anesthesia impacts neurodevelopment or behavioral outcomes, the importance of conducting further large well-designed cohort studies was also emphasized. Adequately powered cohorts could clarify which populations are at increased risk, provide information on environmental and healthcare-related risk modifiers, and guide future interventional trials. If anesthetics cause structural or functional adverse neurological effects in young children, alternative or mitigating strategies need to be considered. While protective or mitigating strategies have been repeatedly studied in animals, there are currently no human data to support alternative anesthetic strategies in clinical practice. Lastly, it was noted that there is still considerable debate over the clinical relevance of anesthesia neurotoxicity, and the need to evaluate the impact of other aspects of perioperative care on neurodevelopment must also be considered.",
keywords = "anesthesia, clinical trial, neurodevelopment, neurotoxicity, pediatrics, research, Anesthesia/adverse effects, Humans, Neurotoxicity Syndromes/etiology, Child Development/drug effects, Brain/drug effects, Animals, Anesthetics/administration & dosage, Child",
author = "Nicola Disma and O'Leary, {James D.} and Loepke, {Andreas W.} and Brambrink, {Ansgar M.} and Karin Becke and Clausen, {Nicola G.} and {De Graaff}, {Jurgen C.} and Fang Liu and Hansen, {Tom G.} and McCann, {Mary E.} and Salorio, {Cynthia F.} and Sulpicio Soriano and Sun, {Lena S.} and Peter Szmuk and Warner, {David O.} and Laszlo Vutskits and Davidson, {Andrew J.}",
note = "{\circledC} 2018 John Wiley & Sons Ltd.",
year = "2018",
month = "9",
day = "1",
doi = "10.1111/pan.13455",
language = "English",
volume = "28",
pages = "758--763",
journal = "Paediatric Anaesthesia",
issn = "1155-5645",
publisher = "Wiley-Blackwell",
number = "9",

}

Disma, N, O'Leary, JD, Loepke, AW, Brambrink, AM, Becke, K, Clausen, NG, De Graaff, JC, Liu, F, Hansen, TG, McCann, ME, Salorio, CF, Soriano, S, Sun, LS, Szmuk, P, Warner, DO, Vutskits, L & Davidson, AJ 2018, 'Anesthesia and the developing brain: A way forward for laboratory and clinical research', Paediatric Anaesthesia, bind 28, nr. 9, s. 758-763. https://doi.org/10.1111/pan.13455

Anesthesia and the developing brain : A way forward for laboratory and clinical research. / Disma, Nicola; O'Leary, James D.; Loepke, Andreas W.; Brambrink, Ansgar M.; Becke, Karin; Clausen, Nicola G.; De Graaff, Jurgen C.; Liu, Fang; Hansen, Tom G.; McCann, Mary E.; Salorio, Cynthia F.; Soriano, Sulpicio; Sun, Lena S.; Szmuk, Peter; Warner, David O.; Vutskits, Laszlo; Davidson, Andrew J.

I: Paediatric Anaesthesia, Bind 28, Nr. 9, 01.09.2018, s. 758-763.

Publikation: Bidrag til tidsskriftReviewForskningpeer review

TY - JOUR

T1 - Anesthesia and the developing brain

T2 - A way forward for laboratory and clinical research

AU - Disma, Nicola

AU - O'Leary, James D.

AU - Loepke, Andreas W.

AU - Brambrink, Ansgar M.

AU - Becke, Karin

AU - Clausen, Nicola G.

AU - De Graaff, Jurgen C.

AU - Liu, Fang

AU - Hansen, Tom G.

AU - McCann, Mary E.

AU - Salorio, Cynthia F.

AU - Soriano, Sulpicio

AU - Sun, Lena S.

AU - Szmuk, Peter

AU - Warner, David O.

AU - Vutskits, Laszlo

AU - Davidson, Andrew J.

N1 - © 2018 John Wiley & Sons Ltd.

PY - 2018/9/1

Y1 - 2018/9/1

N2 - All commonly used general anesthetics have been shown to cause neurotoxicity in animal models, including nonhuman primates. Opinion, however, remains divided over how cumulative evidence from preclinical and human studies in this field should be interpreted and its translation to current practices in pediatric anesthesia and surgery. A group of international experts in laboratory and clinical sciences recently convened in Genoa, Italy, to evaluate the current state of both laboratory and clinical research and discuss future directions for basic, translational, and clinical studies in this field. This paper describes those discussions and conclusions. A central goal identified was the importance of continuing to pursue laboratory research efforts to better understand the biological pathways underlying anesthesia neurotoxicity. The distinction between basic and translational experimental designs in this field was highlighted, and it was acknowledged that it will be important for future animal research to try to causally link structural changes with long-term cognitive abnormalities. While inherent limitations will continue to affect the ability of even large observational cohorts to determine if anesthesia impacts neurodevelopment or behavioral outcomes, the importance of conducting further large well-designed cohort studies was also emphasized. Adequately powered cohorts could clarify which populations are at increased risk, provide information on environmental and healthcare-related risk modifiers, and guide future interventional trials. If anesthetics cause structural or functional adverse neurological effects in young children, alternative or mitigating strategies need to be considered. While protective or mitigating strategies have been repeatedly studied in animals, there are currently no human data to support alternative anesthetic strategies in clinical practice. Lastly, it was noted that there is still considerable debate over the clinical relevance of anesthesia neurotoxicity, and the need to evaluate the impact of other aspects of perioperative care on neurodevelopment must also be considered.

AB - All commonly used general anesthetics have been shown to cause neurotoxicity in animal models, including nonhuman primates. Opinion, however, remains divided over how cumulative evidence from preclinical and human studies in this field should be interpreted and its translation to current practices in pediatric anesthesia and surgery. A group of international experts in laboratory and clinical sciences recently convened in Genoa, Italy, to evaluate the current state of both laboratory and clinical research and discuss future directions for basic, translational, and clinical studies in this field. This paper describes those discussions and conclusions. A central goal identified was the importance of continuing to pursue laboratory research efforts to better understand the biological pathways underlying anesthesia neurotoxicity. The distinction between basic and translational experimental designs in this field was highlighted, and it was acknowledged that it will be important for future animal research to try to causally link structural changes with long-term cognitive abnormalities. While inherent limitations will continue to affect the ability of even large observational cohorts to determine if anesthesia impacts neurodevelopment or behavioral outcomes, the importance of conducting further large well-designed cohort studies was also emphasized. Adequately powered cohorts could clarify which populations are at increased risk, provide information on environmental and healthcare-related risk modifiers, and guide future interventional trials. If anesthetics cause structural or functional adverse neurological effects in young children, alternative or mitigating strategies need to be considered. While protective or mitigating strategies have been repeatedly studied in animals, there are currently no human data to support alternative anesthetic strategies in clinical practice. Lastly, it was noted that there is still considerable debate over the clinical relevance of anesthesia neurotoxicity, and the need to evaluate the impact of other aspects of perioperative care on neurodevelopment must also be considered.

KW - anesthesia

KW - clinical trial

KW - neurodevelopment

KW - neurotoxicity

KW - pediatrics

KW - research

KW - Anesthesia/adverse effects

KW - Humans

KW - Neurotoxicity Syndromes/etiology

KW - Child Development/drug effects

KW - Brain/drug effects

KW - Animals

KW - Anesthetics/administration & dosage

KW - Child

U2 - 10.1111/pan.13455

DO - 10.1111/pan.13455

M3 - Review

C2 - 30117228

AN - SCOPUS:85050358386

VL - 28

SP - 758

EP - 763

JO - Paediatric Anaesthesia

JF - Paediatric Anaesthesia

SN - 1155-5645

IS - 9

ER -