Biological stress markers and neuro-cognitive/psychiatric sequelae in critically ill children
Dr Lorraine Als, Dr Simon Nadel, Prof Elena Garralda
- Start Date:
01 January 2006
Imperial College School of Medicine at St Mary's Hospital, London, UK
Improvements in medical care have reduced mortality from critical illness in childhood. Nevertheless, research by our group has identified high rates of subsequent psychiatric disorders and indications of educational distress following childhood critical illness and severe infection. In addition, results from a pilot study indicate that PICU admission, and more specifically severe infection, may result in neuro-cognitive anomalies particularly affecting memory and learning.
Biological stress associated with critical illness and severe infection may explain neuropsychological and emotional sequelae. Neuro-endocrine changes during the stress response occur acutely, resulting in increased cortisol levels. Animal and human studies have linked high cortisol levels with hippocampal damage. This may affect cognitive function, leading to deficits in verbal recall and declarative memory. Anomalous hypothalamic-pituitary-adrenal axis reactivity and increased cortisol levels have also been connected with stress disorders in children and may underlie both cognitive anomalies and emotional/behavioural changes following severe infection.
Other clinical and biochemical aspects may also be relevant in severe infection. Sepsis is characterized by marked physiological stress. It can lead to septic shock with sympathetic system activation and release of inflammatory cytokines. In addition the condition may necessitate the use of vasoactive and sedative pharmaceutical agents. There may be intracranial infection and immunological changes, which can contribute to alteration in neurological responses and altered cognitive function.
Our pilot study of PICU-admitted children has identified reduced performance in tests measuring visual and verbal memory (spatial working memory and word pairs learning tests), as well as sustained attention (rapid visual information processing test). Visual working memory deficits in this study were linked to behavioural problems, particularly affecting attention and motor activity regulation. In children with severe infection, the study specifically documented decreased performance in tests of visual pattern recognition memory, thought to reflect anomalies in temporal structures, and these were linked to emotional symptoms.
Children, aged 4-16 years, admitted to PICUs or high dependency units in London with severe sepsis and meningo-encephalitis, will be assessed for neuro-psychological sequelae. Performance will be compared 3-6 months following hospital discharge with that of healthy controls. To examine the contribution of sepsis and/or brain involvement to neuro-psychological deficits we will contrast matched groups of children with sepsis, with bacterial meningitis and with other non-septic disorders also leading to PICU and high dependency unit admission. To assess physiological stress response regulation we will contrast levels of cortisol and amylase (biological stress markers) found in the saliva of children admitted to PICU-high dependency with that of healthy controls. We will study associations of neuro-psychological or cognitive performance with specific illness features, psychiatric adjustment, and physiological stress responses. To examine changes in neuro-psychological anomalies over time, we will carry out a 12-month follow-up of a sub-group of children with sepsis and meningitis.
The possible effects of steroids and other biological stress markers on psychological functioning have not previously been explored in a critically ill child population. Understanding these effects better may help explain and eventually alter biological mechanisms determining psychological sequelae.