For better or worse? Long-term outcome of critical illness in childhood

Abstract

The aim of this thesis was to investigate the long-term outcome of critically ill children admitted to the pediatric intensive care unit (PICU) of the Erasmus MC – Sophia Children’s’ Hospital in Rotterdam, the Netherlands. Our main focus was to investigate the long-term health status, health-related quality of life (HR-QoL), emotional and behavioral functioning, and neuropsychological functioning in survivors of cardiac arrest (CA) in childhood. This included a semi-structured interview, physical and neuropsychological examination, and the use of validated, internationally well-known questionnaires with a multi-informant approach. Further, the influence of medical predictor variables, such as the impact of hyperoxia on mortality after CA, and analgesia-sedation on the long-term neuropsychological outcome after a critical illness (specifically meningococcal septic shock) was examined.

In the study described in chapter 2 we analyzed the relationship between the partial pressure of arterial oxygen (PaO2) and in-hospital (IH) mortality in children after CA. We compared the conventional cut-off analysis, with the cumulative analysis, a new method in PaO2 analysis. The innovative aspect of this study is that it uses a novel and simple method (area under the curve) to analyze this cumulative PaO2. We found that patients with mild therapeutic hypothermia (MTH) and higher cumulative PaO2 had a lower mortality rate. With the cumulative PaO2 measurement, we could not reproduce the relationship between higher PaO2 and IH-mortality in children after CA as found in various cut-off studies.

In chapter 3 we provided a detailed overview of the long-term health status and health-related quality of life (HR-QoL) in survivors of CA in childhood and their parents. After the initial survival another 9% died following PICU discharge. A minority of CA survivors showed long-term neurological impairments, chronic symptoms, and renal impairments. On health status and HR-QoL, parent-reports of CA survivors showed significantly worse outcomes on physical scales and parental impact compared to normative data. On self-reports no significant differences with normative data were found. Surprisingly, parents reported better scores towards their own functioning. Patients’ health status, general health perceptions and physical summary scores were significantly associated with CA-related pre-existing condition.

In chapter 4 the results of the long-term emotional and behavioral functioning of CA survivors are presented. Compared to normative data, CA survivors showed significantly more long-term attention problems and somatic complaints, on parents’ and teachers’ reports. On self-reports, significantly less social problems were found. According to parents, children showed more often psychopathological problem behavior. Remarkably, less social problems (self-reports) and no higher levels on anxiety, depression or posttraumatic stress problems were found. Boys, older children, and basic life support were significantly related to worse scores on the scales Internalizing problems, Externalizing problems, Total problems, and subscale Attention problems.

In chapter 5 we described the long-term neuropsychological outcomes in children surviving cardiac arrest (CA). CA survivors scored significantly worse on intelligence. On neuropsychological tests, compared with norms, respectively adjusted for IQ, significantly worse scores were found on visual memory, significantly better on verbal memory recognition, and comparable outcomes on visual-motor integration, attention, and executive functioning. On questionnaires, parents reported better executive functioning, but teachers reported more problems in planning/organizing skills. Boys and older age at time of cardiac arrest were significantly related with worse neuropsychological functioning.

The study presented in chapter 6 investigates the association between analgesic and sedative drug use during PICU treatment and long-term neuropsychological outcome in children who survived meningococcal septic shock. The use and dose of opioids were significantly associated with poor outcome on full-scale IQ, verbal IQ and verbal IQ subtests (verbal comprehension and vocabulary) and visual attention/executive functioning (Trail Making Test B). After adjusting for patient and disease characteristics (in particular severity of illness), the use of opioids remained a significant predictor on most neuropsychological tests. The use and dose of benzodiazepines were not significantly associated with any neuropsychological test.

In chapter 7 we discussed the findings presented in this thesis, put them into perspective and propose recommendations for future studies.