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Turner AD, Sullivan T, Drury K, et al. Cognitive Dysfunction After Analgesia and Sedation: Out of the Operating Room and Into the Pediatric Intensive Care Unit. Front Behav Neurosci. 2021;15:713668doi: 10.3389/fnbeh.2021.713668.
Turner, A. D., Sullivan, T., Drury, K., Hall, T. A., Williams, C. N., Guilliams, K. P., Murphy, S., & Iqbal O'Meara, A. M. (2021). Cognitive Dysfunction After Analgesia and Sedation: Out of the Operating Room and Into the Pediatric Intensive Care Unit. Frontiers in behavioral neuroscience, 15713668. https://doi.org/10.3389/fnbeh.2021.713668
Turner, Ashley D, et al. "Cognitive Dysfunction After Analgesia and Sedation: Out of the Operating Room and Into the Pediatric Intensive Care Unit." Frontiers in behavioral neuroscience vol. 15 (2021): 713668. doi: https://doi.org/10.3389/fnbeh.2021.713668
Turner AD, Sullivan T, Drury K, Hall TA, Williams CN, Guilliams KP, Murphy S, Iqbal O'Meara AM. Cognitive Dysfunction After Analgesia and Sedation: Out of the Operating Room and Into the Pediatric Intensive Care Unit. Front Behav Neurosci. 2021 Aug 16;15:713668. doi: 10.3389/fnbeh.2021.713668. eCollection 2021. PMID: 34483858; PMCID: PMC8415404.
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Front Behav Neurosci. 2021 Aug 16;15:713668. doi: 10.3389/fnbeh.2021.713668. eCollection 2021.

Cognitive Dysfunction After Analgesia and Sedation: Out of the Operating Room and Into the Pediatric Intensive Care Unit.

Frontiers in behavioral neuroscience

Ashley D Turner, Travis Sullivan, Kurt Drury, Trevor A Hall, Cydni N Williams, Kristin P Guilliams, Sarah Murphy, A M Iqbal O'Meara

Affiliations

  1. Division of Pediatric Critical Care, Department of Pediatrics, Washington University in St. Louis, St. Louis, MO, United States.
  2. Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, VA, United States.
  3. Department of Pediatrics, Division of Pediatric Critical Care, Doernbecher Children's Hospital, Oregon Health & Science University, Portland, OR, United States.
  4. Department of Pediatrics, Division of Pediatric Psychology, Pediatric Critical Care and Neurotrauma Recovery Program, Doernbecher Children's Hospital, Oregon Health & Science University, Portland, OR, United States.
  5. Division of Pediatric Neurology, Department of Neurology, Washington University in St. Louis, St. Louis, MO, United States.
  6. Division of Neuroradiology, Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO, United States.
  7. Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
  8. Department of Pediatrics, Child Health Research Institute, Children's Hospital of Richmond at Virginia Commonwealth University School of Medicine, Richmond, VA, United States.
  9. Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD, United States.

PMID: 34483858 PMCID: PMC8415404 DOI: 10.3389/fnbeh.2021.713668

Abstract

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.

Copyright © 2021 Turner, Sullivan, Drury, Hall, Williams, Guilliams, Murphy and Iqbal O’Meara.

Keywords: benzodiazepine; cognitive dysfunction; delirium; neurodevelopment; opioid; pediatric intensive care outcomes; pediatric post-intensive care syndrome; sedative neurotoxicity

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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