Stress symptoms post-PICU; effects of medication and inflammation
Research type
Research Study
Full title
Stress symptoms following paediatric intensive care admission; effects of medication and inflammation
IRAS ID
228504
Contact name
Simon Nadel
Contact email
Sponsor organisation
Imperial College Healthcare NHS Trust
Duration of Study in the UK
3 years, 0 months, 0 days
Research summary
Study summary:
Symptoms of post-traumatic stress disorder (PTSD) have been detected in approximately 30% of children following a paediatric intensive care unit (PICU) admission. There are a number of proposed underlying mechanisms for this finding.PTSD and inflammation
Biological markers within the immune systems of individuals with PTSD demonstrate a skew towards a pro-inflammatory state; they have high levels of markers that are associated with general inflammation (the body’s response to harmful stimuli). It is not clear whether inflammation has a causative role in the development of symptoms or whether it arises alongside or after the symptoms develop. Our pilot study showed that septic illness (a state of substantial inflammation resulting from overwhelming infection) was a risk factor for the development of PTSD. This finding supports the hypothesis that inflammatory processes at the time of acute trauma may be a causative factor.
PTSD and cortisol
A further component in the factors leading to the development of PTSD is a dysregulated stress response. This is mediated by the stress hormone cortisol. Both low and high cortisol levels have been shown in patients with PTSD. Due to clear practical and ethical obstacles, there have been very few studies performed to illustrate the cortisol levels in individuals who go on to develop PTSD whilst they are undergoing acute trauma. It has been proposed that an inadequate cortisol response at the time of trauma may lead to strengthening of the formation of traumatic memories due to the direct effects of cortisol on the memory circuits in the brain. As a number of the symptoms of PTSD involve traumatic memories, these strengthened memories result in greater level of symptoms of the disorder.
Corticosteroid use in PICU
Corticosteroids are medications that act to reduce inflammation and have similar effects in the body to the stress hormone cortisol. They are used in some patients during septic illness. The decision about which patients to use these medications in varies as there has been no clear outcome from a number of studies about which patients benefit from their use. Observational studies in adults have shown reduced PTSD symptoms in those who received corticosteroids. A possible mechanism to explain this is the correction for inappropriately low cortisol and a resultant reduction in the formation of traumatic memories. It is possible that the anti-inflammatory properties of corticosteroids may also contribute.
Our pilot study of 15 children replicated this finding; significantly reduced levels of PTSD intrusion symptoms (the symptoms that are related to traumatic memories) were found in those who received corticosteroids. This study intends to explore this finding on a larger scale
Summary of results:
Objective
Paediatric intensive care unit (PICU) admission represents a traumatic event for many children: short-term follow-up studies have found 10- 30% rates of post traumatic stress disorders (PTSD), and PTSD symptoms have been linked more particularly to admissions for sepsis (overwhelming infection of the body). This study investigates the longer term PTSD outcome of children admitted to PICU with sepsis.Setting & Patients
Children aged >3 years, discharged from one PICU in London following admission for sepsis between 2010 and 2017.Results
Data for 65 participants (48% male, median assessment age 8.0 years) were returned. The average time since admission was 5.1 years. 30.8% of children scored at risk of PTSD at any time since discharge. PTSD symptoms at any time since discharge were significantly associated with acute rise in a marker of inflammation in the blood (known as C-Reactive protein) in the first 48 hours of the admission. Other trauma exposures and female gender were also risk factors.Conclusion
PTSD symptoms in children who have survived sepsis can be persistent. Our findings support a possible role of changes in inflammation in the body alongside the experience of other traumatic events to the development of PTSD.REC name
North West - Greater Manchester West Research Ethics Committee
REC reference
17/NW/0519
Date of REC Opinion
29 Sep 2017
REC opinion
Further Information Favourable Opinion