In the ICU, it is crucial to evaluate the neurological status of pediatric patients effectively. Severe sepsis often leads to an acute disorder of consciousness, highlighting the need for tools to identify these patients and prevent long-term neurological damage.

UNDERSTANDING THE SPECTRUM OF CONSCIOUSNESS

What is coma? Defining terms such as “coma” and “disorder of consciousness” is fundamental to comprehending the impact of sepsis on the brain. The “Curing Coma Campaign” launched by the Neurocritical Care Society in 2020 has sparked growing interest in studying coma in ICUs (1). Disorder of consciousness refers to a state between full consciousness and coma (2–4). Philosophically, consciousness can be defined as wakefulness, sentience, and self-consciousness. Boundaries can be blurred, as wakefulness is contingent upon being awake and normally alert. A sentient nature implies being capable of sensing and responding to the world, while self-consciousness requires “awareness of one own awareness” (5).

From a biomedical standpoint, wakefulness is mediated by the reticular activating system, involving projections from pontine tegmentum, posterior hypothalamus, and thalamus. Awareness, on the other hand, depends on higher cortical and subcortical functions. Coma represents a complete absence of wakefulness and awareness, distinguishing it from other diminished mental states such as a vegetative state or minimally conscious state (6). Acute disorder of consciousness, also known as acute encephalopathy, is a distinct condition occurring in critically ill patients and encompasses delirium, encephalopathies from seizures, and metabolic or infectious causes.

NEUROLOGICAL COMPLICATIONS IN CRITICALLY ILL CHILDREN

Neurological complications in critically ill children pose significant concerns, affecting both short-term and long-term outcomes. Severe sepsis remains a significant threat, with high mortality and morbidity rates. Although sepsis bundles and goal-directed therapies have improved survival, the heterogeneity of sepsis-induced multiple organ failure (MOF) necessitates targeted interventions (7–9). The Phenotyping Sepsis-Induced Multiple Organ Failure Study (PHENOMS) provides valuable insights into the complex interplay between sepsis, organ dysfunction, and neurological manifestations in pediatric patients. The original study showed that a higher extent of central nervous system involvement was associated with increased PICU mortality (10,11). Additionally, machine-learning algorithms identified four distinguishable sepsis phenotypes with variable neurological involvement (12).

THE CURRENT STUDY

In this issue of Pediatric Critical Care Medicine, Cheung et al (13) present a secondary analysis of the PHENOMS dataset, focusing on the neurological impact in pediatric patients. By examining the frequency of acute disorders of consciousness (DoC), defined as a Glasgow Coma Scale (GCS) score of less than 12, and their association with specific sepsis phenotypes, the study emphasizes the necessity for neurologic monitoring and interventions in certain subgroups. This paper contributes to existing knowledge by shedding light on the neurological challenges faced by critically ill children and emphasizes the importance of timely identification and comprehensive care beyond immediate survival.

STUDY FINDINGS AND IMPLICATIONS

The researchers analyzed data from 401 children with severe sepsis and found that 18% of them experienced DoC during their PICU stay. The frequency of DoC was higher among children with MOF compared with those with single organ failure. Among the different sepsis phenotypes, non-phenotypeable MOF and immunoparalysis-associated MOF showed the highest association with DoC. The presence of macrophage activation syndrome and older age increased the odds of DoC, while viral infection decreased the odds.

These findings underscore the importance of recognizing and monitoring neurological manifestations, particularly DoC, in children with severe sepsis and MOF. Children with DoC exhibited higher mortality rates and increased need for advanced interventions like mechanical ventilation and continuous renal replacement therapy. The study also identified macrophage activation syndrome as a significant risk factor for DoC, emphasizing the importance of considering underlying immunologic dysregulation in these patients.

STRENGTHS AND LIMITATIONS

The strength of the study by Cheung et al (13) lies in its rigorous methodology, utilizing a large, multicenter cohort for robust data collection and analysis. However, it is crucial to acknowledge the limitations inherent in its retrospective design, potential biases, and the restriction of findings to specific critical care settings. Moreover, relying on the GCS scores to assess DoC may underestimate its occurrence in infants and toddlers, and the exclusion of sedated patients from the analysis warrants consideration (14). It is essential to develop and validate more refined tools for neurological examinations in ICU patients beyond the GCS. For example, newly developed assessment tools like “serial neurological assessment in pediatrics” or “quick neurological assessment” could offer a more comprehensive evaluation by incorporating communication and cranial nerve function assessment, in addition to consciousness and motor function evaluation (15–17). Last, it is important to note that the study by Cheung et al (13) does not investigate long-term neurological outcomes in the study population, which should be a focus of future research.

IMPLICATIONS FOR CRITICAL CARE PRACTITIONERS

The study’s findings hold significant implications for critical care practitioners. Close monitoring and early detection of neurological dysfunction in critically ill children are essential. Timely recognition of these complications enables targeted interventions that may mitigate long-term cognitive and functional impairments. In particular, the use of multimodal monitoring, including techniques such as electroencephalogram, pupillometry, and near-infrared spectroscopy, can be valuable for assessing patients who do not have a primary neurological problem but are at risk for DoC. Integrating neurological assessments into routine pediatric critical care, using appropriate tools, is vital for proactive identification and management of these challenges. This approach optimizes outcomes and enhances the quality of life for young patients after discharge.

MOVING FORWARD

The PHENOMS study represents a significant milestone in unraveling the intricate relationship between sepsis, organ dysfunction, and neurological manifestations in pediatric patients. By highlighting the frequency of DoC and its association with specific phenotypes, this research emphasizes the importance of neurologic monitoring and interventions in managing pediatric sepsis. Further research is necessary to refine assessment tools, investigate underlying mechanisms, and develop targeted therapies to mitigate the impact of DoC on patient outcomes. Translating these findings into clinical practice holds the promise of improving the long-term prognosis for critically ill children grappling with sepsis-induced MOF.

CONCLUSIONS

Research like the PHENOMS study equips healthcare providers with a heightened understanding of the neurological challenges in the PICU, paving the way for enhanced care, improved outcomes, and brighter futures for our young patients. As we navigate the complex maze of pediatric critical care, it is our responsibility to remain conscious of the importance of neurologic evaluation and interventions, surpassing mere survival and aiming for comprehensive care that addresses long-term implications.

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