A Service evaluation of a hospital child death review process to elucidate understanding of contributory factors to child mortality and inform practice in the English National Health Service.

OBJECTIVE: To describe a novel approach to hospital mortality meetings to elucidate understanding of contributory factors to child death and inform practice in the National Health Service. DESIGN: All child deaths were separately reviewed at a meeting attended by professionals across the healthcare pathway, and an assessment was made of contributory factors to death across domains intrinsic to the child, family and environment, parenting capacity and service delivery. Data were analysed from a centrally held database of records. SETTING: All child deaths in a tertiary children's hospital between 1 April 2010 and 1 April 2013. MAIN OUTCOME MEASURES: Descriptive data summarising contributory factors to child deaths. RESULTS: 95 deaths were reviewed. In 85% cases, factors intrinsic to the child provided complete explanation for death. In 11% cases, factors in the family and environment and, in 5% cases, factors in parenting capacity, contributed to patient vulnerability. In 33% cases, factors in service provision contributed to patient vulnerability and in two patients provided complete explanation for death. 26% deaths were classified as potentially preventable and in those cases factors in service provision were more commonly identified than factors across other domains (OR: 4.89; 95% CI 1.26 to 18.9). CONCLUSIONS: Hospital child death review meetings attended by professionals involved in patient management across the healthcare pathway inform understanding of events leading to a child's death. Using a bioecological approach to scrutinise contributory factors the multidisciplinary team concluded most deaths occurred as a consequence of underlying illness. Although factors relating to service provision were commonly identified, they rarely provided a complete explanation for death. Efforts to reduce child mortality should be driven by an understanding of modifiable risk factors. Systematic data collection arising from a standardised approach to hospital reviews should be the basis for national mortality review processes and database development.

A clinical and economic evaluation of Control of Hyperglycaemia in Paediatric intensive care (CHiP): a randomised controlled trial.

BACKGROUND: Early research in adults admitted to intensive care suggested that tight control of blood glucose during acute illness can be associated with reductions in mortality, length of hospital stay and complications such as infection and renal failure. Prior to our study, it was unclear whether or not children could also benefit from tight control of blood glucose during critical illness. OBJECTIVES: This study aimed to determine if controlling blood glucose using insulin in paediatric intensive care units (PICUs) reduces mortality and morbidity and is cost-effective, whether or not admission follows cardiac surgery. DESIGN: Randomised open two-arm parallel group superiority design with central randomisation with minimisation. Analysis was on an intention-to-treat basis. Following random allocation, care givers and outcome assessors were no longer blind to allocation. SETTING: The setting was 13 English PICUs. PARTICIPANTS: Patients who met the following criteria were eligible for inclusion: ≥ 36 weeks corrected gestational age; ≤ 16 years; in the PICU following injury, following major surgery or with critical illness; anticipated treatment > 12 hours; arterial line; mechanical ventilation; and vasoactive drugs. Exclusion criteria were as follows: diabetes mellitus; inborn error of metabolism; treatment withdrawal considered; in the PICU > 5 consecutive days; and already in CHiP (Control of Hyperglycaemia in Paediatric intensive care). INTERVENTION: The intervention was tight glycaemic control (TGC): insulin by intravenous infusion titrated to maintain blood glucose between 4.0 and 7.0 mmol/l. CONVENTIONAL MANAGEMENT (CM): This consisted of insulin by intravenous infusion only if blood glucose exceeded 12.0 mmol/l on two samples at least 30 minutes apart; insulin was stopped when blood glucose fell below 10.0 mmol/l. MAIN OUTCOME MEASURES: The primary outcome was the number of days alive and free from mechanical ventilation within 30 days of trial entry (VFD-30). The secondary outcomes comprised clinical and economic outcomes at 30 days and 12 months and lifetime cost-effectiveness, which included costs per quality-adjusted life-year. RESULTS: CHiP recruited from May 2008 to September 2011. In total, 19,924 children were screened and 1369 eligible patients were randomised (TGC, 694; CM, 675), 60% of whom were in the cardiac surgery stratum. The randomised groups were comparable at trial entry. More children in the TGC than in the CM arm received insulin (66% vs. 16%). The mean VFD-30 was 23 [mean difference 0.36; 95% confidence interval (CI) -0.42 to 1.14]. The effect did not differ among prespecified subgroups. Hypoglycaemia occurred significantly more often in the TGC than in the CM arm (moderate, 12.5% vs. 3.1%; severe, 7.3% vs. 1.5%). Mean 30-day costs were similar between arms, but mean 12-month costs were lower in the TGC than in CM arm (incremental costs -£3620, 95% CI -£7743 to £502). For the non-cardiac surgery stratum, mean costs were lower in the TGC than in the CM arm (incremental cost -£9865, 95% CI -£18,558 to -£1172), but, in the cardiac surgery stratum, the costs were similar between the arms (incremental cost £133, 95% CI -£3568 to £3833). Lifetime incremental net benefits were positive overall (£3346, 95% CI -£11,203 to £17,894), but close to zero for the cardiac surgery stratum (-£919, 95% CI -£16,661 to £14,823). For the non-cardiac surgery stratum, the incremental net benefits were high (£11,322, 95% CI -£15,791 to £38,615). The probability that TGC is cost-effective is relatively high for the non-cardiac surgery stratum, but, for the cardiac surgery subgroup, the probability that TGC is cost-effective is around 0.5. Sensitivity analyses showed that the results were robust to a range of alternative assumptions. CONCLUSIONS: CHiP found no differences in the clinical or cost-effectiveness of TGC compared with CM overall, or for prespecified subgroups. A higher proportion of the TGC arm had hypoglycaemia. This study did not provide any evidence to suggest that PICUs should stop providing CM for children admitted to PICUs following cardiac surgery. For the subgroup not admitted for cardiac surgery, TGC reduced average costs at 12 months and is likely to be cost-effective. Further research is required to refine the TGC protocol to minimise the risk of hypoglycaemic episodes and assess the long-term health benefits of TGC. TRIAL REGISTRATION: Current Controlled Trials ISRCTN61735247. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 26. See the NIHR Journals Library website for further project information.

Control of hyperglycaemia in paediatric intensive care (CHiP): study protocol.

BACKGROUND: There is increasing evidence that tight blood glucose (BG) control improves outcomes in critically ill adults. Children show similar hyperglycaemic responses to surgery or critical illness. However it is not known whether tight control will benefit children given maturational differences and different disease spectrum. METHODS/DESIGN: The study is an randomised open trial with two parallel groups to assess whether, for children undergoing intensive care in the UK aged

Surfactant for acute respiratory failure in children: where should it fit in our treatment algorithm?

In a recent meta-analysis, surfactant administration in paediatric acute respiratory failure was associated with improved oxygenation, reduced mortality, increased ventilator-free days and reduced duration of ventilation. Surfactant is expensive, however, and its use involves installation of large volumes into the lungs, resulting in transient hypoxia and hypotension in some patients. Many questions also remain unanswered, such the as optimum dosage and the timing of administration of surfactant. The merits of surfactant administration should therefore still be decided on an individual case-by-case basis.

Postnatal changes in pulmonary vein responses to endothelin-1 in the normal and chronically hypoxic lung.

The response of pulmonary arteries to endothelin-1 (ET-1) changes with age in normal pigs and is abnormal in pulmonary hypertension. The purpose of this study was to determine if the same is true of the pulmonary veins. We studied the wall structure and functional response to ET-1 in pulmonary veins from normal pigs from fetal life to adulthood and from pigs subjected to chronic hypobaric hypoxia either from birth for 3 days or from 3 to 6 days of age. In isolated normal veins, the contractile response decreased by 40% between late fetal life and 14 days of age with a concomitant twofold increase in endothelium-dependent relaxant response. The ET(A) antagonist BQ-123 reduced the contractile response significantly more in newborn than older animals, whereas the ET-B antagonist BQ-788 had no effect in fetal animals and maximally increased contraction at 14 days of age. Hypoxic exposure significantly increased pulmonary vein smooth muscle area and contractile response to ET-1. The relaxation response was impaired following hypoxic exposure from birth but not from 3 to 6 days of age. The ET(A) antagonist BQ-123 decreased contractile and increased dilator responses significantly more than in age-matched controls. Thus pulmonary veins show age-related changes similar to those seen in the pulmonary arteries with a decrease in ET(A)-mediated contractile and increase in ET-B-mediated relaxant response with age. Contractile response was also increased in hypoxia as in the arteries. This study suggests that pulmonary veins are involved in postnatal adaptation and the pathogenesis of pulmonary hypertension.

Porcine pulmonary artery and bronchial responses to endothelin-1 and norepinephrine on recovery from hypoxic pulmonary hypertension.

Many infants recovering from acute lung disease and pulmonary hypertension still have evidence of reactive airways disease at one year of age, suggesting longer-term airway effects. We hypothesized that parallel changes in smooth muscle would occur in airways and pulmonary arteries from animals with pulmonary hypertension and during normoxic recovery. Thus, two-hour-old piglets were subjected to 3 d chronic hypobaric hypoxia and 3-d-old piglets were subjected to 11 d hypoxia. Some animals were allowed to recover in room air for 3 or 6 d. The amount of smooth muscle and responses of isolated paired bronchial and pulmonary artery rings to endothelin-1 (ET-1) and norepinephrine were studied at the end of hypoxic exposure, on recovery and in age-matched control animals. In all hypoxia induced pulmonary hypertensive animals, smooth muscle area and ET-1 contractile response was increased in the pulmonary arteries and bronchi. Norepinephrine-induced relaxant response was impaired significantly in both bronchi and pulmonary arteries. After 3 d recovery, pulmonary arterial smooth muscle area decreased by 65%, and ET-1-induced contractile responses were normal for age. In the airways, ET-1 contractile response only normalized after six days and bronchial smooth muscle was still increased. After 6 d recovery pulmonary arterial norepinephrine-induced relaxant response had returned to normal, but bronchial response remained impaired. Thus during pulmonary hypertension, both bronchial and pulmonary arterial smooth muscle area and contractile responses are increased. On recovery, regression of bronchial structural and functional abnormalities is slower than in pulmonary arteries.

Prediction of ventilation weaning outcome: children are not little adults.

Prediction of ventilation weaning outcome in children is important, as unsuccessful extubation increases both morbidity and mortality. Adult weaning criteria are poor predictors of weaning outcome in children for several possible reasons: the length of mechanical ventilation is generally much shorter, and the weaning failure rate is lower in children (thus larger patient numbers are required); integrated weaning indices, such as the rapid shallow breathing index, do not account for normal developmental changes in respiratory function; and the heterogeneity of mechanically ventilated children is greater than in adults. The challenge remains to find universal weaning outcome predictors in children.

Treatment of atelectasis: where is the evidence?

Lobar atelectasis is a common problem caused by a variety of mechanisms including resorption atelectasis due to airway obstruction, passive atelectasis from hypoventilation, compressive atelectsis from abdominal distension and adhesive atelectasis due to increased surface tension. However, evidence-based studies on the management of lobar atelectasis are lacking. Examination of air-bronchograms on a chest radiograph may be helpful to determine whether proximal or distal airway obstruction is involved. Chest physiotherapy, nebulised DNase and possibly fibreoptic bronchoscopy might be helpful in patients with mucous plugging of the airways. In passive and adhesive atelectasis, positive end-expiratory pressure might be a useful adjunct to treatment.

Postnatal changes in response to norepinephrine in the normal and pulmonary hypertensive lung.

The effect of norepinephrine administration on pulmonary blood flow during the neonatal period is unclear. Therefore, norepinephrine responses were studied in isolated pulmonary arteries, pulmonary veins, and femoral arteries taken from normal pigs from birth to adulthood and from pigs subjected to chronic hypoxia either from birth for 3 days or from 3 to 14 days of age. Normally, the contractile response of pulmonary arteries and veins to norepinephrine decreased after birth (p < 0.01), and alpha2-adrenoceptor-mediated relaxation increased in pulmonary arteries and veins and in femoral arteries. Hypoxic exposure from birth prevented the normal postnatal reduction in pulmonary arterial contractile response, nor was there a postnatal increase in pulmonary arterial adrenoceptor-mediated relaxation. When hypoxic exposure followed a period of normal adaptation, the pulmonary arterial contractile response was not enhanced, but relaxation was significantly impaired. The response of pulmonary veins and femoral arteries was not affected by hypoxic exposure. The contractile effect of norepinephrine was 15- to 60-fold greater in isolated systemic arteries than in pulmonary arteries taken from both normal and pulmonary hypertensive piglets at all ages. This suggests that use of norepinephrine to manage systemic hypotension in infants and children will not compromise the pulmonary vasculature.

Do bronchodilators have an effect on bronchiolitis?

Over the past 12 years there have been 12 randomised control trials, involving 843 infants, evaluating the effect of salbutamol or albuterol on bronchiolitis. Of these, nine (75%) showed that bronchodilators had no effect. In three studies a small transient improvement in the acute clinical score was seen. Ipratropium bromide had no significant effect. There have been five recent randomised trials involving 225 infants, evaluating the effect of nebulised adrenaline (epinephrine) on bronchiolitis. All five (100%) have shown significant clinical improvement, with reductions in oxygen requirement, respiratory rate and wheeze after nebulised adrenaline. Two showed lower hospital admission rates and earlier discharge with adrenaline. A significant improvement in pulmonary resistance was observed after nebulised adrenaline but not after salbutamol or albuterol. Currently there is no compelling evidence that bronchodilators have a role in the routine management of infants with bronchiolitis. There is better evidence for the use of nebulised adrenaline.