Barry Wilkins

Acute lung injury in pediatric intensive care in Australia and New Zealand: a prospective, multicenter, observational study

Objective: Acute lung injury (ALI) is poorly defined in children. The objective of this prospective study was to clarify the incidence, demographics, management strategies, outcome, and mortality predictors of ALI in children in Australia and New Zealand. Design: Multicenter prospective study during a 12-month period. Setting: Intensive care unit. Patients: All children admitted to intensive care and requiring mechanical ventilation were screened daily for development of ALI based on American-European Consensus Conference guidelines. Identified patients were followed for 28 days or until death or discharge. Interventions: None. Measurements and Main Results: There were 117 cases of ALI during the study period, giving a population incidence of 2.95/100,000 <16 yrs. ALI accounted for 2.2% of pediatric intensive care unit admissions. Mortality was 35% for ALI, and this accounted for 30% of all pediatric intensive care unit deaths during the study period. Significant preadmission risk factors for mortality were chronic disease, older age, and immunosuppression. Predictors of mortality during admission were ventilatory requirements (peak inspiratory pressures, mean airway pressure, positive end-expiratory pressure) and indexes of respiratory severity on day 1 (Pao2/Fio2 ratio and oxygenation index). Higher maximum and median tidal volumes were associated with reduced mortality, even when corrected for severity of lung disease. Development of single and multiple organ failure was significantly associated with mortality. Conclusions: ALI in children is uncommon but has a high mortality rate. Risk factors for mortality are easily identified. Ventilatory variables and indexes of lung severity were significantly associated with mortality.

Glucose control, organ failure, and mortality in pediatric intensive care

Objective: In ventilated children, to determine the prevalence of hyperglycemia, establish whether it is associated with organ failure, and document glycemic control practices in Australasian pediatric intensive care units (PICUs). Design: Prospective inception cohort study. Setting: All nine specialist PICUs in Australia and New Zealand. Patients: Children ventilated >12 hrs excluding those with diabetic ketoacidosis, on home ventilation, undergoing active cardiopulmonary resuscitation on admission, or with do-not-resuscitate orders. Interventions: None. Measurements and Main Results: All blood glucose measurements for up to 14 days, clinical and laboratory values needed to calculate Paediatric Logistic Organ Dysfunction (PELOD) scores, and insulin use were recorded in 409 patients. Fifty percent of glucose measurements were >6.1 mmol/L, with 89% of patients having peak values >6.1 mmol/L. The median time to peak blood glucose was 7 hrs. Hyperglycemia was defined by area under the glucose-time curve >6.1 mmol/L above the sample median. Thirteen percent of hyperglycemic subjects died vs. 3% of nonhyperglycemic subjects. There was an independent association between hyperglycemia and a PELOD score ≥10 (odds ratio 3.41, 95% confidence interval 1.91–6.10) and death (odds ratio 3.31, 95% confidence interval 1.26–7.7). Early hyperglycemia, defined using only glucose data in the first 48 hrs, was also associated with these outcomes but not with PELOD ≥10 after day 2 or with worsening PELOD after day 1. Five percent of patients received insulin. Conclusions: Hyperglycemia is common in PICUs, occurs early, and is independently associated with organ failure and death. However, early hyperglycemia is not associated with later or worsening organ failure. Australasian PICUs seldom use insulin.

Hypothermia for traumatic brain injury in children - a Phase II randomized controlled trial

Objectives:To perform a pilot study to assess the feasibility of performing a phase III trial of therapeutic hypothermia started early and continued for at least 72 hours in children with severe traumatic brain injury. Design:Multicenter prospective randomized controlled phase II trial. Setting:All eight of the PICUs in Australia and New Zealand and one in Canada. Patients:Children 1–15 years old with severe traumatic brain injury and who could be randomized within 6 hours of injury. Interventions:The control group had strict normothermia to a temperature of 36–37°C for 72 hours. The intervention group had therapeutic hypothermia to a temperature of 32–33°C for 72 hours followed by slow rewarming at a rate compatible with maintaining intracranial pressure and cerebral perfusion pressure. Measurements and Main Results:Of 764 children admitted to PICU with traumatic brain injury, 92 (12%) were eligible and 55 (7.2%) were recruited. There were five major protocol violations (9%): three related to recruitment and consent processes and two to incorrect temperature management. Rewarming took a median of 21.5 hours (16–35 hr) and was performed without compromise in the cerebral perfusion pressure. There was no increase in any complications, including infections, bleeding, and arrhythmias. There was no difference in outcomes 12 months after injury; in the therapeutic hypothermia group, four (17%) had a bad outcome (pediatric cerebral performance category, 4–6) and three (13%) died, whereas in the normothermia group, three (12%) had a bad outcome and one (4%) died. Conclusions:Early therapeutic hypothermia in children with severe traumatic brain injury does not improve outcome and should not be used outside a clinical trial. Recruitment rates were lower and outcomes were better than expected. Conventional randomized controlled trials in children with severe traumatic brain injury are unlikely to be feasible. A large international trials group and alternative approaches to trial design will be required to further inform practice.

Burden of disease and change in practice in critically ill infants with bronchiolitis.

Bronchiolitis represents the most common cause of non-elective admission to paediatric intensive care units (ICUs). We assessed changes in admission rate, respiratory support, and outcomes of infants <24 months with bronchiolitis admitted to ICU between 2002 and 2014 in Australia and New Zealand. During the study period, bronchiolitis was responsible for 9628 (27.6%) of 34 829 non-elective ICU admissions. The estimated population-based ICU admission rate due to bronchiolitis increased by 11.76 per 100 000 each year (95% CI 8.11–15.41). The proportion of bronchiolitis patients requiring intubation decreased from 36.8% in 2002, to 10.8% in 2014 (adjusted OR 0.35, 95% CI 0.27–0.46), whilst a dramatic increase in high-flow nasal cannula therapy use to 72.6% was observed (p<0.001). We observed considerable variability in practice between units, with six-fold differences in risk-adjusted intubation rates that were not explained by ICU type, size, or major patient factors. Annual direct hospitalisation costs due to severe bronchiolitis increased to over USD30 million in 2014. We observed an increasing healthcare burden due to severe bronchiolitis, with a major change in practice in the management from invasive to non-invasive support that suggests thresholds to admittance of bronchiolitis patients to ICU have changed. Future studies should assess strategies for management of bronchiolitis outside ICUs. Changing thresholds to admit bronchiolitis patients to PICU have had a major impact on cost and resource utilisation http://ow.ly/AVA630a08rx

Use of intravenous salbutamol in acute severe asthma

Sellers & Messahel [1] in their paper report on seven patients (four of whom were children) with acute severe asthma managed in the conventional manner but who in addition received an immediate dose of intravenous salbutamol. They report good clinical response by these patients to intravenous salbutamol although two patients (one a child) eventually required intubation and assisted ventilation. From this experience, these authors suggest that the immediate use of intravenous salbutamol should be considered in every case of acute severe asthma and that if this had little clinical effect, a repeat dose of intravenous salbutamol should be immediately given, and in some cases several times over. The severe asthmatic is easily recognised, but creating an all-encompassing definition of asthma severity has been difficult [2]. There is no single investigation that defines asthma. This has resulted in much confusion in the literature with regards to asthma management. In many cases, what is considered moderate asthma in the southern hemisphere is commonly classified as severe elsewhere. The management of these patients is clearly very different and any attempt at comparison will result in confusion. Most countries now have national guidelines [3] that are in agreement, but we must remain careful in interpreting data that have classified asthma in a non-discriminate way as we are most likely comparing ‘apples with oranges’. A recent meta-analysis on the use of intravenous b-agonists suffers from poor case definition as well and being poorly controlled for patient age. In addition, the study combines papers that use both b-agonists and aminophylline in treatment protocols that were so different as to be considered different approaches to management rather than equivalent therapies [4]. The paper by Sellers & Messahel again raises the perennial question of asthma definition and how they defined acute severe asthma in their report. In our original paper on the use of intravenous salbutamol in children [5], there was a difference between severe as defined in that paper, i.e. severe enough to come to the emergency department and not responding to the first dose of inhaled salbutamol, and that in the general asthma literature. Sellers & Messahel have defined severe asthma in the traditional way as used by PICU, these patients having refractory disease with significant respiratory failure mandating intensive care. Asthma is an inflammatory disease that is typified by airway hyper reactivity and obstruction, producing variable airway resistance with a reduction in air flow [5]. The initial management of an acute attack involves a stepwise approach, although in cases of life-threatening asthma immediate intravenous therapy is recommended [6]. Traditionally, intravenous therapy, particularly in children, has been left for the most severe cases. This is often considered after the use of frequent doses of inhaled bronchodilators has failed. In cases of severe asthma, any delay in clinical response may render airways bronchodilator unresponsive due to progression of the inflammatory process in these airways. We believe there is a window of opportunity during initial presentation with severe asthma to the emergency department where the airways may continue to be bronchodilator responsive. If intravenous therapy is used early as shown by Sellers et al., then clinical response should be rapid with more rapid stabilisation of the patient. The mainstay of treatment of acute asthma involves the frequent use of inhaled b-agonists, together with corticosteroids [6]. We have shown that inhaled b-agonists produce systemic plasma drug concentrations in the range 20–40 ng.ml, within 2 h of commencement of therapy. In many patients, but particularly in children, with severe asthma, inhaled therapy can be unreliable as this is dependent on delivery technique and tidal volume, both of which are highly variable [5, 7, 8]. In addition, these patients fail to improve because severe bronchospasm and mucus plugging prevents distal drug delivery by the aerosol route. In this case, a better initial alternative, particularly if asthma is severe, is to use the intravenous route. Intravenous b-agonist therapy can be highly effective in reversing bronchospasm, even in the presence of marked hypercapnia [9]. It has been shown that intravenous salbutamol was more effective than inhaled salbutamol in reversing airways obstruction. In addition, those patients receiving the intravenous preparation achieved earlier therapeutic level, more rapid clinical response and could be discharged earlier. With intravenous salbutamol, plasma levels similar to those achieved with inhaled therapy are reached with a 10-min infusion of salbutamol at a rate of 1.5 lg.kg.min [5, 7, 8]. We would ideally recommend in children that intravenous bronchodilator therapy be reserved for patients with acute severe asthma who are not responding to initial nebulised bronchodilators (Fig. 1). The tendency, however, to delay intravenous drug treatment in the most severe asthmatic patients has the potential to lead to a protracted clinical course. Sellers & Messahel suggest in their paper that if after initial intravenous bolus no clinical effect is observed, repeated boluses of intravenous salbutamol should be considered. This is probably safe provided the patient is carefully monitored in the presence of an intensive care physician. In our institution, we would use a short-term continuous intravenous salbutamol infusion, commencing this in the emergency department. Although widely Anaesthesia, 2003, 58, pages 729–733 .....................................................................................................................................................................................................................

A fatal case of hypernatraemic dehydration in a neonate

Problems with lactation can result in hypernatraemic dehydration in the neonate, with potentially severe adverse consequences. This is illustrated in this fatal case of a 10 day old neonate who presented with excessive hypernatraemic dehydration due to insufficient breast milk intake, resulting in cerebral sinus vein thrombosis with cerebral haemorrhage and infarction. Differential diagnosis included excessive sodium intake (through inappropriately mixed formula or house remedies or through hyperaldosteronism) and high water deficit (renal or gastrointestinal losses, nephrogenic or central diabetes insipidus), all of which were ruled out by specific investigations or history. No evidence was found for inborn error of metabolism. The dehydration in this baby, however, was accentuated by trans‐epidermal water loss due to an ichthyosiform skin condition. This first ever reported Australian fatality from neonatal hypernatraemic dehydration supports the concern of health care professionals over rising incidences of this entity in exclusively breastfed infants, and should encourage endorsement of improved monitoring of weight loss in newborns and breastfeeding support for their mothers.

Abstract P-374: BASE EXCESS CONTAINS USEFUL INFORMATION ABOUT NET NON-LACTATE METABOLIC ACID/BASE STATUS FOR MORTALITY PREDICTION

A single-centre dataset of 6212 PICU admissions with measurement on admission of pH, Bicarbonate, BE, Lactate, Chloride, Albumin, Phosphate, Sodium, Potassium, Calcium and Magnesium (all mEq/L) was analysed to calculate PBE and its components. Non-Lactate BE (i.e. BE+Lactate, since Lactate contributes negatively to BE) was compared with non-Lactate PBE, calculated accurately from its components.

Outcomes of paediatric critical care asthma patients

The aim of this study was to characterise patients with asthma admitted to an Australian paediatric intensive care unit (PICU).

Supraventricular tachycardia as a presenting feature of volvulus in a 15-month-old boy

A 15‐month‐old boy presented in shock with a supraventricular tachycardia following a 12‐h history of worsening abdominal pain and vomiting. The supraventricular tachycardia reverted to sinus tachycardia with fluid resuscitation and adenosine. He was noted to have a distended and firm abdomen. A presumptive diagnosis of intestinal ischaemia was subsequently confirmed at laparotomy when an internal hernia with a distal small bowel volvulus and necrosis was found. Intestinal ischaemia presenting with a life‐threatening cardiac dysrhythmia in a child appears not to have been reported previously.