Pediatric Post-intensive Care Syndrome: Can Transforming Pediatric Sedation Strategies Improve Outcomes?

Amid concerns for potential neurodevelopmental effects following surgical anesthesia, there is also a growing body of evidence in the literature that children who require sedation during critical illness are susceptible to neurologic dysfunctions collectively termed pediatric post-intensive care syndrome or PICS-p.

The clinical challenge

In addition to invasive testing and monitoring, PICU patients often require complex medical procedures which tend to be painful and anxiety-provoking. This necessitates the administration of analgesia and sedation to reduce the stress response.

However, a patient population with a wide spectrum of ages, sizes, and developmental stages presents a considerable challenge to the anesthesia provider to meet the optimal combination of adequate analgesia and appropriate sedation. The added complexities of critical illness in the PICU population including impaired organ function, evolving pathophysiology, as well as altered pharmacodynamics and pharmacokinetics, must be considered.

Over and under risk

Both undersedation and oversedation put critically ill pediatric patients at high risk of developing PICU-acquired complications (PACs) such as delirium, withdrawal syndrome, neuromuscular atrophy and weakness, post-traumatic stress disorder, and poor rehabilitation.

Oversedation can leave patients at risk of needing prolonged respiratory support, prolonged ICU stay and hospital admission, and a higher risk of untoward effects of analgosedative agents.

On the other hand, under sedation leaves patients at risk of physical and psychological stress which may hold significant long-term consequences.

The PICU frontier

In this recent review in the August issue of the journal Frontiers in Behavioral Neuroscience, the authors examine what they deem to be “the next frontier in pediatric intensive care,” that is, “the interactive role of sedatives and the neurologic vulnerability of critically ill children as it pertains to survivorship and functional outcomes.”

Their examination of existing literature enumerates the ways in which the cognitive dysfunction of children who survive their injury or critical illness do not resemble the typical pediatric anesthesia population—and they counsel caution in projecting what is known about cognitive dysfunction following surgical anesthesia in well children to this unique and more complex cohort.

“Results from this body of work should be cautiously applied to the pediatric intensive care population if at all.”

While acknowledging that critical illness is a complex paradigm in which to directly link causative factors with cognitive outcomes following discharge, they cite “multivariate analyses from adults and children [which] consistently identify intensive care sedation and opioid analgesia as important and independent contributors.”

Age-relative risk

Furthermore, while enumerating the limitations to date on the measurement of cognitive outcomes in PICU survivors—including the newness of the understanding of the PICS-p phenomenon itself—the authors highlight the essential relevance of considering patients’ age and developmental stage in assessing the impact of prolonged administration of analgesics and sedatives.

“Children in the PICU are treated with analgesics and sedatives for prolonged periods during the neurologic stress of critical illness during sensitive periods of neurodevelopment.  Mammalian models show notable impact on neurogenesis, synaptogenesis, and myelination suggesting that younger children may be more vulnerable than older children to the effects of analgesics and sedatives based on how brains are built over time via the developmental process.”

Sedation and sleep

Another detrimental result of many PICU sedation regimens, the authors note, is that while critical illness itself is known to disrupt patients’ sleep, there is polysomnographic and EEG evidence that reveals “significant fragmentation and alteration in sleep architecture” in critically ill patients administered analgesics and sedatives.

They also note the sustained impact of these sleep disturbances, citing a 2015 study by Als et al.  “In a long-term follow-up study of pediatric critical illness, survivors suffered significantly more sleep problems than healthy controls and 72% scored at high risk for sleep disorders.”

Change agents

As part of their call for further study of the impact of sedation and analgesia approaches on these vulnerable PICU patients, the authors conclude that these protocols are among the only variables that may have the potential to improve their post-discharge cognitive outcomes.

“…While age and illness factors cannot be changed, analgesia and sedation are potentially modifiable, and a better understanding of the discrete contribution of these drugs in the larger context of critical illness is sorely needed.”

Access this comprehensive review, “Cognitive Dysfunction After Analgesia and Sedation: Out of the Operating Room and Into the Pediatric Intensive Care Unit.” Front Behav Neurosci. 2021;15:713668, at no cost at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415404/