Lactate, Base Excess, and the Pediatric Index of Mortality: Exploratory Study of an International, Multicenter Dataset.

OBJECTIVES: To investigate the relationship between ICU admission blood lactate, base excess, and ICU mortality and to explore the effect of incorporating blood lactate into the Pediatric Index of Mortality. DESIGN: Retrospective cohort study based on data prospectively collected on every PICU admission submitted to the U.K. Pediatric Intensive Care Audit Network and to the Australia and New Zealand Pediatric Intensive Care Registry. SETTING: Thirty-three PICUs in the United Kingdom/Republic of Ireland and nine PICUs and 20 general ICUs in Australia and New Zealand. PATIENTS: All ICU admissions between January 1, 2012, and December 31, 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred twenty-three thousand two hundred fifty-two admissions were recorded in both datasets; 81,576 (66.2%) in the United Kingdom/Republic of Ireland and 41,676 (33.8%) in Australia and New Zealand. Of these 75,070 (61%) had a base excess recorded, 63,316 (51%) had a lactate recorded, and 60,876 (49%) had both base excess and lactate recorded. Median lactate value was 1.5 mmol/L (interquartile range, 1-2.4 mmol/L) (United Kingdom/Republic of Ireland: 1.5 [1-2.5]; Australia and New Zealand: 1.4 [1-2.3]). Children with a lactate recorded had a higher illness severity, were more likely to be invasively ventilated, admitted after cardiac surgery, and had a higher mortality rate, compared with admissions with no lactate recorded (p < 0.001). The relationship between lactate and mortality was stronger (odds ratio, 1.32; 95% CI, 1.31-1.34) than between absolute base excess and mortality (odds ratio, 1.13; 95% CI, 1.12-1.14). Addition of lactate to the Pediatric Index of Mortality score led to a small improvement in performance over addition of absolute base excess, whereas adding both lactate and absolute base excess achieved the best performance. CONCLUSIONS: At PICU admission, blood lactate is more strongly associated with ICU mortality than absolute base excess. Adding lactate into the Pediatric Index of Mortality model may result in a small improvement in performance. Any improvement in Pediatric Index of Mortality performance must be balanced against the added burden of data capture when considering potential incorporation into the Pediatric Index of Mortality model.

Diagnosis and incidence of acute kidney injury in a mixed paediatric intensive care unit: Retrospective analysis, 2005 and 2015.

Acute kidney injury (AKI) is common in intensive care patients. While creatinine definitions for AKI have been validated, oliguria criteria are less well evaluated in children. Our study compared the validity and agreement of creatinine and oliguria criteria for diagnosing AKI in a large mixed medical, surgical and cardiac paediatric intensive care unit (PICU), and assessed the significance of their independent and combined effects on predicted mortality relative to paediatric index of mortality (PIM risk of death) on admission. Creatinine measurements during PICU admissions in 2005 and 2015 were obtained from the electronic medical record. Urine output was reviewed to identify periods of oliguria of more than eight hours. We used the PIM3 model for predicted risk of death. AKI based on creatinine rise occurred in 23.6% of the total 2203 admissions (10.0%, 8.2% and 5.6% for mild, moderate and severe categories, respectively). Oliguria occurred in 11.4% (8.4%, 1.8% and 1.2% for mild, moderate and severe categories, respectively) and overlapped only partially with creatinine criteria. Mortality relative to predicted mortality increased with increasing creatinine and oliguria severity, but was lower than predicted where oliguria occurred without creatinine rise. AKI by creatinine criteria and/or oliguria are common in the PICU, but criteria overlap only partially. Increasing severity of creatinine rise and oliguria confers increasing risk-adjusted mortality, especially for admissions with low PIM3 risk of death. The mortality of patients with AKI defined by oliguria alone is low. Defining AKI by oliguria alone has less clinical utility and may not represent true AKI.

RACHS - ANZ : A Modified Risk Adjustment in Congenital Heart Surgery Model for Outcome Surveillance in Australia and New Zealand.

Background Outcomes for pediatric cardiac surgery are commonly reported from international databases compiled from voluntary data submissions. Surgical outcomes for all children in a country or region are less commonly reported. We aimed to describe the bi-national population-based outcome for children undergoing cardiac surgery in Australia and New Zealand and determine whether the Risk Adjustment for Congenital Heart Surgery ( RACHS ) classification could be used to create a model that accurately predicts in-hospital mortality in this population. Methods and Results The study was conducted in all children's hospitals performing cardiac surgery in Australia and New Zealand between January 2007 and December 2015. The performance of the original RACHS -1 model was assessed and compared with an alternative RACHS - ANZ (Australia and New Zealand) model, developed balancing discrimination with parsimonious variable selection. A total of 14 324 hospital admissions were analyzed. The overall hospital mortality was 2.3%, ranging from 0.5% for RACHS category 1 procedures, to 17.0% for RACHS category 5 or 6 procedures. The original RACHS -1 model was poorly calibrated with death overpredicted (1161 deaths predicted, 289 deaths observed). The RACHS - ANZ model had better performance in this population with excellent discrimination (Az- ROC of 0.830) and acceptable Hosmer and Lemeshow goodness-of-fit ( P=0.216). Conclusions The original RACHS -1 model overpredicts mortality in children undergoing heart surgery in the current era. The RACHS - ANZ model requires only 3 risk variables in addition to the RACHS procedure category, can be applied to a wider range of patients than RACHS -1, and is suitable to use to monitor regional pediatric cardiac surgery outcomes.

Outcomes of paediatric critical care asthma patients.

AIM: The aim of this study was to characterise patients with asthma admitted to an Australian paediatric intensive care unit (PICU). METHODS: This was a retrospective review of patients with asthma admitted to a university-affiliated, 23-bed, tertiary PICU between January 2000 and December 2011, with a subset of pharmacotherapy and biochemical data from patients admitted between July 2007 and December 2011. RESULTS: A total of 589 admissions (501 patients) with asthma over 12 years constituted 4.4% of all PICU admissions. Three patients died (0.6%). Non-invasive ventilation (NIV) was used in 104 (17.7%) admissions, and 41 (7%) were invasively ventilated. On 12 (2%) occasions, patients received both NIV and invasive ventilation. Over 12 years, there was a significant trend to increased use of NIV, 11-39% (P < 0.0001), and invasive ventilation, 6-14% (P < 0.001). All received steroids and nebulised ß2-agonists. A total of 92% received intravenous (IV) ß2-agonists, 65% of these for less than 12 h. PICU and hospital stay were proportional to the duration of IV ß2-agonist infusion (P < 0.0001). A total of 47.1% received IV magnesium sulphate, increasing from 19 to 75% (P < 0.001). The majority (48%) were transferred directly to PICU from other hospitals. Median PICU stay was 1.04 days (0.72-1.63); hospital stay was 3.16 days (2.29-4.71), and both were unchanged. CONCLUSIONS: Intensive care length of stay (LOS) was unchanged over 12 years. Both invasive and NIV and IV magnesium sulphate use increased. LOS was directly related to the duration of IV ß2-agonist. Asthma patients admitted to PICU typically have a brief stay and have a fairly predictable course. Prospective studies could explore the contribution of IV agents and the role of NIV.

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.

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.

Sodium administration in critically ill paediatric patients in Australia and New Zealand: a multicentre point prevalence study.

OBJECTIVE: Dysnatraemia and a positive fluid balance are associated with poor outcomes in paediatric intensive care units (PICUs). Our objective was to determine sodium intake and the total daily fluid balance in children in the PICU. METHOD: A single-day point prevalence study in 10 Australian and New Zealand PICUs. Patients on free oral diets were excluded. Demographics, 24-hour fluid balance and sodium intake (enteral and parenteral sources) were recorded. RESULTS: We enrolled 65 patients; 15 were excluded due to having a free oral intake and two patients had incomplete data, leaving 48 children in the study cohort. The 21 infants had a median age of 4 months (interquartile range [IQR], 1-7 months) and a median bodyweight of 5 kg (IQR, 3.5- 6.1 kg). The 27 children > 1 year had a median age of 3 years (IQR, 1.5-13 years) and a median bodyweight of 17 kg (IQR, 9.5-47.5 kg). Overall, the median sodium administration on the study day was 4.9mmol/kg (IQR, 3.2- 8mmol/kg), median fluid administration was 80.8mL/kg (IQR, 49.8-111.4mL/kg) and median fluid balance was 9mL/kg (IQR, -1.4 to 41 mL/kg). For infants, the median sodium administration was 6mmol/kg (IQR, 3.9-8.1mmol/ kg), and median fluid balance was 20.8mL/kg (IQR, 3.5- 47.2mL/kg). For children > 1 year, the median sodium administration was 3.5mmol/kg (IQR, 3.1-7.8mmol/kg), and median fluid balance was 5.3mL/kg (IQR, -2.7 to 17.7mL/kg). Overall, fluid infusions, boluses and catheter flushes together contributed 46.2% of total sodium administered. Drugs contributed substantially to administered sodium (33.3%), with antibiotics accounting for the majority. Enteral feeds contributed 16.2% to overall administered sodium, and were the major source in patients in the PICU for > 10 days. CONCLUSION: Daily sodium intake in children in the PICU is high. The contributions of maintenance and bolus intravenous fluids (most commonly as 0.9% sodium chloride), drug infusions and boluses, including antibiotics, and enteral feeds, are significant.

Ventilator-associated pneumonia in a tertiary paediatric intensive care unit: a 1-year prospective observational study.

OBJECTIVES: To determine the incidence, risk factors and impact of ventilator-associated pneumonia (VAP) in a mixed tertiary paediatric intensive care unit. DESIGN: Prospective observational study. METHODS: Patients in the intensive care unit who were mechanically ventilated for more than 48 hours were assessed daily, according to criteria for a diagnosis of VAP. Potential risk factors for VAP, if present, were documented. RESULTS: Of 692 invasively ventilated patients, 269 (38.9%) were ventilated for > 48 hours and met no exclusion criteria. Eighteen (6.7%) patients had episodes of VAP, and the VAP incidence density was 7.02 per 1000 intubation days. The mean admission Paediatric Index of Mortality 2 risk of death was similar in patients with and without VAP (0.084 v 0.056; P =0.8). Patients with VAP (compared with patients without VAP) had a longer median duration of ICU stay, (19.35 v 7.35 days; P < 0.001), duration of ventilation (11.99 v 4.92 days; P=0.024) and duration of hospital stay (35.5 v 20 days; P < 0.001). Univariate analysis showed that reintubation, absence of tube feeding and absence of stress ulcer prophylaxis were risk factors for VAP. While backward selection removed reintubation as a positive predictor during multivariate analysis, tube feeds (hazard ratio (HR), 0.27; 95% CI, 0.09-0.85; P = 0.02) and stress ulcer prophylaxis (HR, 0.29; 95% CI, 0.11-0.76; P = 0.01) were independently associated with reduced VAP incidence. CONCLUSIONS: VAP in children is associated with significant morbidity and increased length of hospital stay. Enteral feeding and stress ulcer prophylaxis while intubated are associated with lower VAP hazards.

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.

Increase in use of non-invasive ventilation for infants with severe bronchiolitis is associated with decline in intubation rates over a decade.

PURPOSE: To redress the paucity of studies evaluating non-invasive respiratory support in bronchiolitis patients. METHODS: Following ethics committee approval, the clinical database of a tertiary 23-bed paediatric intensive care unit (PICU) was reviewed for bronchiolitis admissions from January 2000 to December 2009. Length of stay (LOS), ventilatory requirements and risk factors, including prematurity, respiratory syncytial virus (RSV) status, chronic lung, neuromuscular, immune and congenital heart disease, were analysed. RESULTS: Of 8,288 admissions, 520 (6.27 %) had bronchiolitis with 343 (65.9 %) having RSV. Median (±SD) age and LOS were 2.78 months and 2.68 (±4.32) days. One (0.2 %) patient died. Assisted ventilation was required for 399 (76.7 %) patients. A total of 114 (28.6 %) patients were intubated directly and 285 (71.4 %) had a trial of non-invasive ventilation (NIV). Significant increase in the use of NIV was seen (2.8 %/year) with decline in intubation rates (1.9 %/ year) (p = 0.002). Of NIV patients, 237 (83.2 %) needed only NIV and 48 (16.8 %) failed and therefore needed intubation. The median LOS was shorter in those who succeeded NIV (2.38 ± 2.43 days) compared to those with invasive ventilation (5.19 ± 6.34 days) and those who failed NIV (8.41 ± 3.44 days). Presence of a risk factor increased the chances of failing NIV from 6 to 10 %. CONCLUSION: NIV was successful in the vast majority of patients, particularly in those without risk factors and halved the LOS in intensive care. Failure of NIV was associated with increased duration of invasive ventilation and PICU LOS. A prospective study comparing different techniques of NIV will be helpful in defining the risks of failure of NIV.

Human renal function maturation: a quantitative description using weight and postmenstrual age.

This study pools published data to describe the increase in glomerular filtration rate (GFR) from very premature neonates to young adults. The data comprises measured GFR (using polyfructose, (51)Cr-EDTA, mannitol or iohexol) from eight studies (n = 923) and involved very premature neonates (22 weeks postmenstrual age) to adulthood (31 years). A nonlinear mixed effects approach (NONMEM) was used to examine the influences of size and maturation on renal function. Size was the primary covariate, and GFR was standardized for a body weight of 70 kg using an allometric power model. Postmenstrual age (PMA) was a better descriptor of maturational changes than postnatal age (PNA). A sigmoid hyperbolic model described the nonlinear relationship between GFR maturation and PMA. Assuming an allometric coefficient of 3/4, the fully mature (adult) GFR is predicted to be 121.2 mL/min per 70 kg [95% confidence interval (CI) 117-125]. Half of the adult value is reached at 47.7 post-menstrual weeks (95%CI 45.1-50.5), with a Hill coefficient of 3.40 (95%CI 3.03-3.80). At 1-year postnatal age, the GFR is predicted to be 90% of the adult GFR. Glomerular filtration rate can be predicted with a consistent relationship from early prematurity to adulthood. We propose that this offers a clinically useful definition of renal function in children and young adults that is independent of the predictable changes associated with age and size.

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.

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 > or = 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 > or = 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.

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.