Albert P. Bos

Experimentally induced congenital diaphragmatic hernia in rats.

Experiments to induce congenital diaphragmatic hernia (CDH) in rats, by means of administering a single dose of 2,4-dichlorophenyl-P-nitrophenyl (Nitrofen) on the 10th day of gestation, are reported here. Previously, congenital diaphragmatic hernia has been induced in sheep late in fetal development, and in mice early in gestation. The rat model, including a control group, was used to evaluate lung development and the presence of lung hypoplasia by morphometrical analysis. It was found that the single dose of Nitrofen, given 5 days before the normal closure of the diaphragm in the rat, leads to a high incidence of diaphragmatic hernia, mainly on the right side, and highly abnormal lung development (hypoplasia) comparable to the human situation. Both the lung weight/body weight index as well as the radial alveolar count were significantly lower in animals with CDH (P less than .05). This animal model offers a good opportunity to study abnormal lung development in relation to ventilatory capacity and pulmonary vascular reactivity.

Congenital diaphragmatic hernia: Impact of preoperative stabilization. A prospective pilot study in 13 patients

In case of congenital diaphragmatic hernia (CDH), survival generally depends not on prenatal diagnosis, planned delivery, and immediate postnatal operation, but on the gravity of pulmonary hypoplasia and persistent hypertension (PPH). Many vasoactive drugs have become available for lowering PPH, but the mortality rate for CDH still amounts to 40% to 70%. Preoperative stabilization might prevent or at least reduce the risk of PPH. This method was evaluated in a pilot study lasting 15 months and involving 13 patients. All were admitted to the pediatric surgical intensive care unit within six hours of birth, all requiring mechanical ventilation. Continuous suction of the stomach and bowel proved successful in reducing the mediastinal shift. Study parameters were alveolar-arterial oxygenation differences ((A-a)DO2), mean airway pressure (MAP), oxygenation index (OI), and ventilation index (VI), measured on admission and at set times before and after surgery. Eight patients did not survive, but in two cases death was not directly related to CDH. The following conclusions were reached: (1) satisfactory ventilation parameters on admission will remain good during the preoperative stabilization phase and will not be affected by its duration or by subsequent surgery, spelling survival; (2) unsatisfactory ventilation parameters on admission may improve with preoperative stabilization, giving these patients a better chance of survival; and (3) poor ventilation parameters on admission that fail to improve with preoperative stabilization will not improve with surgery or postoperatively, spelling death.

Quality of life in children three and nine months after discharge from a paediatric intensive care unit: a prospective cohort study

BackgroundImproved survival in children with critical illnesses has led to new disease patterns. As a consequence evaluation of the well being of survivors of Pediatric Intensive Care Units (PICU) has become important. Outcome assessment should therefore consist of evaluation of morbidity, functional health and Health Related Quality of Life (HRQoL). Awareness of HRQoL consequences and physical sequelae could lead to changes in support during the acute phase and thereafter. The aim of this study was to evaluate HRQoL in PICU survivors.MethodsProspective follow-up study three and nine months after discharge from a 14-bed tertiary PICU. Eighty-one of 142 eligible, previously healthy children were included from December 2002 through October 2005. HRQoL was assessed with the TNO-AZL Preschool Children Quality of Life Questionnaire (TAPQOL-PF) for children aged 1 to 6 years of age, the TNO-AZL Childrens Quality of Life Questionnaire Parent Form (TACQOL-PF) for children aged 6 to 12 years of age, and the TNO-AZL Childrens Quality of Life Questionnaire Child Form (TACQOL-CF) for children aged 8 to 15 years of age. The studied patients were compared with age appropriate normative data using non-parametric tests and effect sizes.ResultsThirty-one and 27 children, and 55 and 50 parents completed questionnaires respectively three and nine months after discharge. In 1–6 year old children parents reported more lung problems (3 and 9 months), worse liveliness (9 months) and better appetite and problem behaviour (3 months); in 6–12 year old children parents reported worse motor functioning (3 months); and 12–15 year old adolescents reported worse motor functioning (3 months). Large effect sizes indicating clinical significant differences in HRQoL with healthy control subjects were found on more domains.ConclusionIn this small group of PICU survivors differences in HRQoL with the normative population exist three and nine months after discharge. Calculated effect sizes were smaller nine months after discharge. These changes suggest that HRQoL improves over time. More research is necessary but we believe that HRQoL assessment should be incorporated in follow-up programs of PICU survivors.

Follow‐up after paediatric intensive care treatment: parental posttraumatic stress

Aim: To study the prevalence of posttraumatic stress in parents after an acute admission to a paediatric intensive care unit (PICU) and to determine risk factors for the development of posttraumatic stress.

Course and Predictors of Posttraumatic Stress Disorder in Parents after Pediatric Intensive Care Treatment of their Child

OBJECTIVE To study posttraumatic stress disorder (PTSD) in parents after unexpected pediatric intensive care unit (PICU) treatment of their child and to identify risk factors for its development. METHOD Parents completed PTSD questionnaires 3 and 9 months (N = 190) after PICU treatment. Risk factors included pretrauma data, medical data, social demographics and posttraumatic stress responses at 3 months. RESULTS In total, 30.3% of parents met criteria for subclinical PTSD and 12.6% for clinical PTSD at 3 months. Clinical PTSD prevalence rates did not change over time. At 9 months, 10.5% of parents still met criteria for PTSD. Number of earlier stressful life events, earlier psychosocial care and posttraumatic stress responses at 3 months predicted persistent subclinical and clinical PTSD. CONCLUSIONS PICU admission is a stressful event associated with persistent parental PTSD. Assessment of risk factors can facilitate detection of persistent PTSD for early intervention.

Immune complex associated complications in the subacute phase of meningococcal disease: incidence and literature review

Aim: To determine the incidence of immune complex associated complications (IAC) after severe meningococcal disease (SMD) in a group of Dutch children admitted to a paediatric intensive care unit (PICU). Methods: Retrospective chart analysis and follow up of 130 survivors of SMD admitted to PICU. Signs of IAC, inflammatory parameters, and temperature profile were reviewed. Results: Of 130 children with SMD, 20 (15.3%) showed one or more of the three manifestations of IAC: 18 (13.8%) developed arthritis (effusion, with or without erythema/arthralgia), 11 (8.4%) vasculitis, and five (3.8%) pleuritis. Eighteen of 20 (90%) patients with IAC had a secondary rise in temperature; in patients with no IAC this was 48 of 110 (43.6%). IAC was associated with leucocytosis in 82.3% versus 47.7% in patients without IAC, and with increased CRP in 86.6% versus 47.2% in patients without IAC. Leucocytes on admission were significantly lower in patients who would later develop IAC (mean 8.6 versus 13.8×109/l). Conclusion: IAC is a common complication of SMD, mainly occurring 4–10 days after systemic disease. IAC presents clinically as arthritis or vasculitis, mostly accompanied by secondary fever and raised inflammatory parameters.

Outcome of paediatric intensive care survivors

The development of paediatric intensive care has contributed to the improved survival of critically ill children. Physical and psychological sequelae and consequences for quality of life (QoL) in survivors might be significant, as has been determined in adult intensive care unit (ICU) survivors. Awareness of sequelae due to the original illness and its treatment may result in changes in treatment and support during and after the acute phase. To determine the current knowledge on physical and psychological sequelae and the quality of life in survivors of paediatric intensive care, we undertook a computerised comprehensive search of online databases for studies reporting sequelae in survivors of paediatric intensive care. Studies reporting sequelae in paediatric survivors of cardiothoracic surgery and trauma were excluded, as were studies reporting only mortality. All other studies reporting aspects of physical and psychological sequelae were analysed. Twenty-seven studies consisting of 3,444 survivors met the selection criteria. Distinct physical and psychological sequelae in patients have been determined and seemed to interfere with quality of life. Psychological sequelae in parents seem to be common. Small numbers, methodological limitations and quantitative and qualitative heterogeneity hamper the interpretation of data. We conclude that paediatric intensive care survivors and their parents have physical and psychological sequelae affecting quality of life. Further well-designed prospective studies evaluating sequelae of the original illness and its treatment are warranted.

Acute respiratory distress syndrome leads to reduced ratio of ACE/ACE2 activities and is prevented by angiotensin‐(1–7) or an angiotensin II receptor antagonist

Acute respiratory distress syndrome (ARDS) is a devastating clinical syndrome. Angiotensin‐converting enzyme (ACE) and its effector peptide angiotensin (Ang) II have been implicated in the pathogenesis of ARDS. A counter‐regulatory enzyme of ACE, ie ACE2 that degrades Ang II to Ang‐(1–7), offers a promising novel treatment modality for this syndrome. As the involvement of ACE and ACE2 in ARDS is still unclear, this study investigated the role of these two enzymes in an animal model of ARDS. ARDS was induced in rats by intratracheal administration of LPS followed by mechanical ventilation. During ventilation, animals were treated with saline (placebo), losartan (Ang II receptor antagonist), or with a protease‐resistant, cyclic form of Ang‐(1–7) [cAng‐(1–7)]. In bronchoalveolar lavage fluid (BALF) of ventilated LPS‐exposed animals, ACE activity was enhanced, whereas ACE2 activity was reduced. This was matched by enhanced BALF levels of Ang II and reduced levels of Ang‐(1–7). Therapeutic intervention with cAng‐(1–7) attenuated the inflammatory mediator response, markedly decreased lung injury scores, and improved lung function, as evidenced by increased oxygenation. These data indicate that ARDS develops, in part, due to reduced pulmonary levels of Ang‐(1–7) and that repletion of this peptide halts the development of ARDS. Copyright

Posttraumatic stress disorder (PTSD) in children after paediatric intensive care treatment compared to children who survived a major fire disaster

BackgroundThe goals were to determine the presence of posttraumatic stress disorder (PTSD) in children after paediatric intensive care treatment, to identify risk factors for PTSD, and to compare this data with data from a major fire disaster in the Netherlands.MethodsChildren completed the Dutch Childrens Responses to Trauma Inventory at three and nine months after discharge from the paediatric intensive care unit (PICU). Comparison data were available from 355 children survivors who completed the same questionnaire 10 months after a major fire disaster.ResultsThirty-six children aged eight to 17 years completed questionnaires at three month follow-up, nine month follow-up, or both. More than one third (34.5%) of the children had subclinical PTSD, while 13.8% were likely to meet criteria for PTSD. Maternal PTSD was the strongest predictor for child PTSD. There were no significant differences in (subclinical) PTSD symptoms either over time or compared to symptoms of survivors from the fire disaster.ConclusionThis study shows that a considerable number of children have persistent PTSD after PICU treatment. Prevention of PTSD is important to minimize the profound adverse effects that PTSD can have on childrens well-being and future development.

An explorative study on quality of life and psychological and cognitive function in pediatric survivors of septic shock.

Objective: To evaluate self-reported health-related quality of life, anxiety, depression, and cognitive function in pediatric septic shock survivors. Design: A retrospective cohort study. Setting: A 14-bed tertiary pediatric intensive care unit. Patients: Children aged ≥8 yrs at the time of the follow-up who were admitted between 1995 and 2004 for septic shock. Inotropic and or vasoconstrictive agents were administered to these patients for ≥24 hrs. Intervention: Health-related quality of life was assessed with the KIDSCREEN-52, anxiety with the State Trait Anxiety Inventory for Children, depression with the Childrens Depression Inventory, and cognitive function with the cognitive scale of the TNO-AZL Childrens Quality of Life Questionnaire Child Form. Measurements and Main Results: Fifty of 82 eligible pediatric septic shock survivors were evaluated. The median age of the children at pediatric intensive care unit admission was 4.2 yrs (range, 0.0–17.0 yrs); the median age at follow-up was 10.7 yrs (range, 8.0–20.4 yrs). Health-related quality of life and anxiety scores were comparable to the age-related Dutch norm population. Depression scores were significantly better than the norm population, whereas cognitive function was significantly lower than the norm population. We found that 44% of the children had cognitive scores <25% of the norm population. Young age at the time of pediatric intensive care unit admission was predictive of cognitive problems, and cognitive problems were associated with lower emotional function. Conclusions: In this group of septic shock survivors, health-related quality of life, anxiety, and depression are equal to or slightly better than the age-related Dutch norm population. Cognitive function is decreased, especially in children admitted at younger ages. Follow-up studies with adequate neuropsychological testing are warranted to evaluate the association between septic shock, cognitive function, and risk factors for cognitive problems.