TY - JOUR
T1 - Cognitive Dysfunction After Analgesia and Sedation
T2 - Out of the Operating Room and Into the Pediatric Intensive Care Unit
AU - Turner, Ashley D.
AU - Sullivan, Travis
AU - Drury, Kurt
AU - Hall, Trevor A.
AU - Williams, Cydni N.
AU - Guilliams, Kristin P.
AU - Murphy, Sarah
AU - Iqbal O’Meara, A. M.
N1 - Funding Information:
CW was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number K23HL150229. AI was supported by the Children’s Hospital Foundation of Richmond through a pediatric neuroscience program grant. Publications costs were supported by the Division of Pediatric Critical Care Medicine, Children’s Hospital of Richmond at Virginia Commonwealth University.
Funding Information:
We would like to acknowledge the editorial assistance of Amanda Furman. Figures have been created with BioRender.com. Funding. CW was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number K23HL150229. AI was supported by the Children?s Hospital Foundation of Richmond through a pediatric neuroscience program grant. Publications costs were supported by the Division of Pediatric Critical Care Medicine, Children?s Hospital of Richmond at Virginia Commonwealth University.
Publisher Copyright:
© Copyright © 2021 Turner, Sullivan, Drury, Hall, Williams, Guilliams, Murphy and Iqbal O’Meara.
PY - 2021/8/16
Y1 - 2021/8/16
N2 - In the midst of concerns for potential neurodevelopmental effects after surgical anesthesia, there is a growing awareness that children who require sedation during critical illness are susceptible to neurologic dysfunctions collectively termed pediatric post-intensive care syndrome, or PICS-p. In contrast to healthy children undergoing elective surgery, critically ill children are subject to inordinate neurologic stress or injury and need to be considered separately. Despite recognition of PICS-p, inconsistency in techniques and timing of post-discharge assessments continues to be a significant barrier to understanding the specific role of sedation in later cognitive dysfunction. Nonetheless, available pediatric studies that account for analgesia and sedation consistently identify sedative and opioid analgesic exposures as risk factors for both in-hospital delirium and post-discharge neurologic sequelae. Clinical observations are supported by animal models showing neuroinflammation, increased neuronal death, dysmyelination, and altered synaptic plasticity and neurotransmission. Additionally, intensive care sedation also contributes to sleep disruption, an important and overlooked variable during acute illness and post-discharge recovery. Because analgesia and sedation are potentially modifiable, understanding the underlying mechanisms could transform sedation strategies to improve outcomes. To move the needle on this, prospective clinical studies would benefit from cohesion with regard to datasets and core outcome assessments, including sleep quality. Analyses should also account for the wide range of diagnoses, heterogeneity of this population, and the dynamic nature of neurodevelopment in age cohorts. Much of the related preclinical evidence has been studied in comparatively brief anesthetic exposures in healthy animals during infancy and is not generalizable to critically ill children. Thus, complementary animal models that more accurately “reverse translate” critical illness paradigms and the effect of analgesia and sedation on neuropathology and functional outcomes are needed. This review explores the interactive role of sedatives and the neurologic vulnerability of critically ill children as it pertains to survivorship and functional outcomes, which is the next frontier in pediatric intensive care.
AB - In the midst of concerns for potential neurodevelopmental effects after surgical anesthesia, there is a growing awareness that children who require sedation during critical illness are susceptible to neurologic dysfunctions collectively termed pediatric post-intensive care syndrome, or PICS-p. In contrast to healthy children undergoing elective surgery, critically ill children are subject to inordinate neurologic stress or injury and need to be considered separately. Despite recognition of PICS-p, inconsistency in techniques and timing of post-discharge assessments continues to be a significant barrier to understanding the specific role of sedation in later cognitive dysfunction. Nonetheless, available pediatric studies that account for analgesia and sedation consistently identify sedative and opioid analgesic exposures as risk factors for both in-hospital delirium and post-discharge neurologic sequelae. Clinical observations are supported by animal models showing neuroinflammation, increased neuronal death, dysmyelination, and altered synaptic plasticity and neurotransmission. Additionally, intensive care sedation also contributes to sleep disruption, an important and overlooked variable during acute illness and post-discharge recovery. Because analgesia and sedation are potentially modifiable, understanding the underlying mechanisms could transform sedation strategies to improve outcomes. To move the needle on this, prospective clinical studies would benefit from cohesion with regard to datasets and core outcome assessments, including sleep quality. Analyses should also account for the wide range of diagnoses, heterogeneity of this population, and the dynamic nature of neurodevelopment in age cohorts. Much of the related preclinical evidence has been studied in comparatively brief anesthetic exposures in healthy animals during infancy and is not generalizable to critically ill children. Thus, complementary animal models that more accurately “reverse translate” critical illness paradigms and the effect of analgesia and sedation on neuropathology and functional outcomes are needed. This review explores the interactive role of sedatives and the neurologic vulnerability of critically ill children as it pertains to survivorship and functional outcomes, which is the next frontier in pediatric intensive care.
KW - benzodiazepine
KW - cognitive dysfunction
KW - delirium
KW - neurodevelopment
KW - opioid
KW - pediatric intensive care outcomes
KW - pediatric post-intensive care syndrome
KW - sedative neurotoxicity
UR - http://www.scopus.com/inward/record.url?scp=85114357368&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85114357368&partnerID=8YFLogxK
U2 - 10.3389/fnbeh.2021.713668
DO - 10.3389/fnbeh.2021.713668
M3 - Review article
AN - SCOPUS:85114357368
VL - 15
JO - Frontiers in Behavioral Neuroscience
JF - Frontiers in Behavioral Neuroscience
SN - 1662-5153
M1 - 713668
ER -