Mehrengise Cooper

Fulminant pertussis: a multi-center study with new insights into the clinico-pathological mechanisms.

Pertussis carries a high risk of mortality in very young infants. The mechanism of refractory cardio‐respiratory failure is complex and not clearly delineated. We aimed to examine the clinico‐pathological features and suggest how they may be related to outcome, by multi‐center review of clinical records and post‐mortem findings of 10 patients with fulminant pertussis (FP). All cases were less than 8 weeks of age, and required ventilation for worsening respiratory symptoms and inotropic support for severe hemodynamic compromise. All died or underwent extra corporeal membrane oxygenation (ECMO) within 1 week. All had increased leukocyte counts (from 54 to 132 × 109/L) with prominent neutrophilia in 9/10. The post‐mortem demonstrated necrotizing bronchitis and bronchiolitis with extensive areas of necrosis of the alveolar epithelium. Hyaline membranes were present in those cases with viral co‐infection. Pulmonary blood vessels were filled with leukocytes without well‐organized thrombi. Immunodepletion of the thymus, spleen, and lymph nodes was a common feature. Other organisms were isolated as follows; 2/10 cases Para influenza type 3, 2/10 Moraxella catarrhalis, 1/10 each with respiratory syncytial virus (RSV), a coliform organism, methicillin‐resistant Staphylococcus aureus (MRSA), Haemophilus influenzae, Stenotrophomonas maltophilia, methicillin‐sensitive Staphylococcus aureus (MSSA), and candida tropicalis. We postulate that severe hypoxemia and intractable cardiac failure may be due to the effects of pertussis toxin, necrotizing bronchiolitis, extensive damage to the alveolar epithelium, tenacious airway secretions, and possibly leukostasis with activation of the immunological cascade, all contributing to increased pulmonary vascular resistance. Cellular apoptosis appeared to underlay much of these changes. The secondary immuno‐compromise may facilitate co‐infection. Pediatr Pulmonol. 2009; 44:970–980. ©2009 Wiley‐Liss, Inc.

Neuropsychologic function three to six months following admission to the PICU with meningoencephalitis, sepsis, and other disorders: a prospective study of school-aged children.

Objective:To assess short-term neuropsychological function and academic performance in school children following admission to intensive care and to explore the role of critical neurologic and systemic infection. Design:A prospective observational case–control study. Setting:Two PICUs. Subjects:A consecutive sample of 88 children aged 5–16 years (median age = 10.00, interquartile range = 6.00–13.00) who were admitted to intensive care between 2007 and 2010 with meningoencephalitis, septic illness, or other critical illnesses. They were assessed 3 to 6 months following discharge, and their performance was compared with that of 100 healthy controls. Patients were without prior neurologic or neurodevelopmental disorder. Interventions:None. Measurements and Main Results:Data encompassing demographic and critical illness details were obtained, and children were assessed using tests of intellectual function, memory, and attention. Questionnaires addressing academic performance were returned by teachers. After adjusting for covariates, the children admitted to PICUs significantly underperformed on neuropsychological measures in comparison to healthy controls (p < 0.02). Teachers deemed more children admitted to PICUs than controls as performing educationally worse and having problems with school work (ps = 0.001), as well as performing below average on aspects of executive function and attention (ps < 0.04). Analysis of the effect of illness type on outcome revealed that aspects of neuropsychological function, such as memory function, and teacher-rated academic performance were most reduced in children with meningoencephalitis and septic illness. In the PICU group, multivariable linear regression revealed that worse performance on a composite score of neuropsychologic impairment was more prevalent when children were younger, from a lower social class, and had experienced seizures during their admission (ps < 0.02). Conclusions:Admission to intensive care is followed by deficits in neuropsychologic performance and educational difficulties, with more severe difficulties noted following meningoencephalitis and septic illness. These results highlight the importance of future studies on cognition and educational outcome incorporating type of illness as a moderating factor.

Mental and Physical Well-Being Following Admission to Pediatric Intensive Care

Objective: To assess mental and physical well-being in school-aged children following admission to pediatric intensive care and to examine risk factors for worse outcome. Design: A prospective cohort study. Setting: Two PICUs. Subjects: A consecutive sample of 88 patients 5–16 years old (median age, 10.00 yr; interquartile range, 6.00–13.00 yr) admitted to PICU from 2007 to 2010 with septic illness, meningoencephalitis, or other critical illnesses were assessed a median of 5 months following discharge and outcomes compared with 100 healthy controls. Interventions: None. Measurements and Main Results: Parents completed questionnaires documenting child mental and physical well-being, including the Strengths and Difficulties Questionnaires, Chalder Fatigue Scale, and Child Sleep Habits Questionnaire. Children over 8 years completed the Impact of Event Scale -8. The children admitted to PICU scored worse on all measures in comparison with the healthy controls, with 20% scoring at risk for psychiatric disorder, 34% with high levels of post-traumatic stress symptoms, 38% at risk for fatigue disorder, and 80% scoring at risk for sleep disturbance. In the PICU group, multivariable regression analyses identified septic illness as an independent predictor of post-traumatic stress symptoms and family status, past child health problems, and PICU length of stay as predictors of reduced general mental well-being. Conclusions: Our findings indicate that a significant minority of school-aged children admitted to PICU are at risk for reduced mental and physical well-being in the short term. Symptoms of poor mental well-being were linked to both vulnerability factors and critical illness factors.

Isoflurane for life-threatening bronchospasm: a 15-year single-center experience.

BACKGROUND: Children with severe bronchospasm requiring mechanical ventilation may become refractory to conventional therapy. In these critically ill patients, isoflurane is an inhaled anesthetic agent available in some centers to treat bronchospasm. We hypothesized that isoflurane is safe and would lead to improved gas exchange in children with life-threatening bronchospasm refractory to conventional therapy. METHODS: A retrospective review was conducted and included mechanically ventilated children treated with isoflurane in a quaternary pediatric ICU for life-threatening bronchospasm, from 1993 to 2007. Demographic, blood gas, ventilator, and outcome data were collected. RESULTS: Thirty-one patients, with a mean age of 9.5 years (range 0.4–23 years) were treated with isoflurane, from 1993 to 2007. Mean time to initiation of isoflurane after intubation was 13 hours (0–120 h), and the mean maximum isoflurane dose was 1.1% (0.3–2.5%). Mean duration of isoflurane administration was 54.5 hours (range 1–181 h), with a total mean duration of mechanical ventilation of 252 hours (range 16–1,444 h). Isoflurane led to significant improvement in pH and PCO2 within 4 hours of initiation (P ≤ .001). Complications during isoflurane administration included hypotension requiring vasoactive infusions in 24 (77%), arrhythmia in 3 (10%), neurologic side effects in 3 (10%), and pneumothorax in 1 (3%) patient. CONCLUSIONS: Isoflurane led to improvement in pH and PCO2 within 4 hours in this series of mechanically ventilated patients with life-threatening bronchospasm. The majority of patients in this series developed hypotension, but there was a low incidence of other side effects related to isoflurane administration. Isoflurane appears to be an effective therapy in patients with life-threatening bronchospasm refractory to conventional therapy. However, further investigation is warranted, given the uncertain overall impact of isoflurane in this context.

Persistence of Neuropsychological Deficits Following Pediatric Critical Illness.

Objective:To study 12-month persistence of neuropsychological deficits in PICU survivors. Design:Prospective follow-up study. Setting:Two PICUs. Participants:Children 5–16 years old with neuropsychological deficits 3–6 months following PICU care for meningoencephalitis, sepsis, and other critical illnesses (excluding other primary neurological disorders). Interventions:None. Measurements and Main Results:Neuropsychological function was assessed using the Cambridge Neuropsychological Test Automated Battery, the Children’s Memory Scale, and the Wechsler Abbreviated Scale of Intelligence or Wide Range Intelligence Test. Forty-seven of 88 PICU admitted children (53%) were identified as neuropsychologically impaired 3–6 months after discharge; of these, 23 provided 12-month follow-up data. In spite of significant improvements in measures of memory, there was little change in intelligence quotient and visual attention over the study period, and children’s educational progress remained below expectation. Conclusions:We found persistently reduced neuropsychological function following PICU admission in the critical illnesses under study.

A supported psychoeducational intervention to improve family mental health following discharge from paediatric intensive care: feasibility and pilot randomised controlled trial

Objective To assess feasibility and pilot a supported psychoeducational tool to improve parent and child mental health following discharge from a paediatric intensive care unit (PICU), in preparation for a large randomised controlled trial (RCT). Design Feasibility assessment and single-centre, parallel group, pilot RCT. A concealed computer generated list was used to randomise participants, with an allocation of 2:1 in favour of the intervention. Setting A PICU in an acute care hospital in London, UK. Participants 31 parents of children aged 4–16 years-old admitted to PICU. Intervention Parents received a psychoeducational tool supported by a telephone call. The psychoeducational tool outlined the possible psychological reactions in children and parents alongside management advice. The telephone call addressed each familys postdischarge experience, reinforced the psychoeducational material and encouraged parents to put into practice the advice given. Main outcome measures The primary outcome was the number of feasibility criteria successfully met (linked to the intervention and the study design). Secondary outcomes were questionnaire data collected at 3–6-month follow-up assessing mental health in parents and children. Results 31 parents were randomised (intervention n=22; treatment as usual, TAU n=9). 23 parents were included in the analysis of secondary outcomes (intervention n=17; TAU n=6). 3 (of 6) intervention and 1 (of 6) study design feasibility criteria were fully met. All unmet criteria could be addressed with minor or significant modifications to the protocol. At follow-up there was a tendency for parents who received the intervention to report lower post-traumatic stress symptoms in themselves and fewer emotional and behavioural difficulties in their children than TAU parents. This needs to be explored in a fully powered trial. Conclusions This feasibility and pilot RCT provided valuable information on the intervention and trial design for a full RCT. Trials registration number NCT01737021; Results.

Joint Paediatric and Psychiatric Follow-Up for Families following Paediatric Intensive Care Unit Admission: An Exploratory Study

Psychopathology in parents and children is increased after Paediatric Intensive Care Unit (PICU) admission; few studies have evaluated interventions to reduce this. Objective. Evaluation of the feasibility of setting up a joint paediatric and psychiatric follow-up clinic for families after PICU discharge. Design. Feasibility study offering joint follow-up with a consultant paediatric intensivist and child and adolescent psychiatrist. Setting. Paediatric outpatient clinic in a university teaching hospital with a PICU. Patients. Children and their families discharged from PICU. Interventions. Outpatient appointment focussing on physical and psychological health; psychoeducation about emotional and behavioural difficulties occurring after PICU discharge, advice for parents about supporting their child’s psychological recovery, screening for more severe psychiatric disorders, and provision of a leaflet outlining possible difficulties and management strategies. Measurements. Attendance, content of discussion, psychiatric questionnaires, and family feedback. Main Results. It proved feasible to set up follow-up appointments to address physical and psychological health concerns; 4/12(33%) eligible families attended. Children and mothers who attended all reported child difficulties including sleep disturbance, increased anxiety, and PTSD symptoms in children and parents. Conclusions. Follow-up clinics after PICU discharge are feasible to set up; take-up is poor but families attending report psychopathology which may be addressed through the intervention.

Post-traumatic stress after PICU and corticosteroid use

Aim To examine the association between corticosteroid use in paediatric intensive care units (PICU) and subsequent symptoms of post-traumatic stress disorder (PTSD). Methods The subjects were children aged 8–16 years admitted to PICU with sepsis, meningoencephalitis (ME) and other disorders. Illness information was extracted from case notes; 3–6 months post discharge children completed a PTSD symptom questionnaire (eight-item Impact of Events Scale (IES-8)) assessing intrusion and avoidance symptoms. Saliva samples were also collected for cortisol profile analysis. Results 53 children completed the IES-8 questionnaires. 33 provided saliva samples. 19 (36%) received corticosteroids. In children with sepsis (n=15), corticosteroid use was associated with significantly lower PTSD intrusion symptom scores. There was a trend towards an association between corticosteroid use and lower evening cortisol levels. There was a comparable but weaker trend in children with ME. Discussion Corticosteroid use may be associated with fewer PTSD symptoms and lower evening cortisol levels following PICU admission in children with sepsis.

PS-137a A Brief Intervention To Improve Parent Post-traumatic Stress Symptoms Following Paediatric Critical Illness: A Pilot Randomised Controlled Trial

Background and aims Admission to paediatric intensive care (PIC) has been linked to subsequent post-traumatic stress symptoms (PTSS) in parents. This study aimed to obtain initial estimates regarding the effect of a brief intervention on parent PTSS and explore the mediating effect of baseline parental stress. Methods Parents of children aged 4–16 years old were randomised to intervention versus treatment as usual (TAU). The intervention was delivered within six weeks of discharge from hospital and included a psycho-educational booklet and telephone call. Parents’ baseline stress was measured using the Parental Stressor Scale: PICU. Parents were followed-up a median of 5 months post discharge from PICU and measures of PTSS were obtained using the Impact of Events Scale. Results Although not statistically significant, parents in the intervention group (n = 17) fared better than parents in the TAU group (n = 6): They reported fewer PTSS [19.47 (95% CI 11.64–26.62) vs. 25.83 (95% CI 11.47–39.00)] and fewer were at risk for clinical disorder (18% vs. 33%) (Cohen’s d = 0.38 and 0.34 respectively). However, there were potential implications for screening: “High stress” parents in the intervention group had lower PTSS scores than “high stress” TAU parents (d = 1.06), whereas “low stress” parents in the intervention group had higher PTSS scores than “low stress” TAU parents (d = 0.47) (See Figure 1). Abstract PS-137a Figure 1 Post-traumatic stress symptoms in parents at 5 months post PICU discharge in the intervention (Rx) and Treatment as usual [TAU] groups, split according to baseline parental stress score (H=high stress; L=low stress) Conclusions Pilot data indicate that a brief intervention could have a significant impact on parent PTSS following paediatic critical illness, but this needs to be evaluated in a sufficiently powered RCT.

Cisatracurium in "weakening doses" assists in weaning from sedation and withdrawal following extended use of inhaled isoflurane.

Objective: Isoflurane was used to treat a patient with status asthmaticus refractive to standard therapeutic measures. The patient developed a significant withdrawal syndrome when the isoflurane was weaned. A case is reported here where this withdrawal syndrome was treated successfully by using a weakening dose neuromuscular blockade with cisatracurium. Design: Case report. Setting: Pediatric critical care unit. Patient: A 4-yr-old girl with severe reactive airways disease. Interventions: The use of weakening doses of cisatracurium to assist in weaning from mechanical ventilation in the setting of withdrawal symptoms following the extended use of inhaled isoflurane. Measurements and Main Results: Despite treatment with mechanical ventilation, intravenous corticosteroids, and bronchodilators for status asthmaticus, the patient required inhaled isoflurane. She became tolerant to isoflurane over an extended period of time; her tolerance was associated with a specific withdrawal syndrome, with the development of choreoathetoid movements resulting in poor pulmonary coordination and agitation. Conventional medical treatment of withdrawal failed. Finally, by using an infusion of cisatracurium at weakening doses to assist in the control of these choreoathetoid movements, the isoflurane and ventilator support were weaned. Conclusions: Weakening doses of cisatracurium may be used safely to control unpleasant motor symptoms secondary to tolerance of isoflurane. This may have a use in other circumstances where agitation in mechanically ventilated patients is not due to pain or anxiety.