Association Between Centralization and Outcome for Children Admitted to Intensive Care in Australia and New Zealand: A Population-Based Cohort Study.

OBJECTIVES: To describe regional differences and change over time in the degree of centralization of pediatric intensive care in Australia and New Zealand (ANZ) and to compare the characteristics and ICU mortality of children admitted to specialist PICUs and general ICUs (GICUs). DESIGN: A retrospective cohort study using registry data for two epochs of ICU admissions, 2003-2005 and 2016-2018. SETTING: Population-based study in ANZ. PATIENTS: A total of 43,256 admissions of children aged younger than 16 years admitted to an ICU in ANZ were included. Infants aged younger than 28 days without cardiac conditions were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was risk-adjusted ICU mortality. Logistic regression was used to investigate the association of mortality with the exposure to ICU type, epoch, and their interaction. Compared with children admitted to GICUs, children admitted to PICUs were younger (median 25 vs 47 mo; p < 0.01) and stayed longer in ICU (median 1.6 vs 1.0 d; p < 0.01). For the study overall, 93% of admissions in Australia were to PICUs whereas in New Zealand only 63% of admissions were to PICUs. The adjusted odds of death in epoch 2 relative to epoch 1 decreased (adjusted odds ratio [AOR], 0.50; 95% CI, 0.42-0.59). There was an interaction between unit type and epoch with increased odds of death associated with care in a GICU in epoch 2 (AOR, 1.63; 95% CI, 1.05-2.53 for all admissions; 1.73, CI, 1.002-3.00 for high-risk admissions). CONCLUSIONS: Risk-adjusted mortality of children admitted to specialist PICUs decreased over a study period of 14 years; however, a similar association between time and outcome was not observed in high-risk children admitted to GICUs. The results support the continued use of a centralized model of delivering intensive care for critically ill children.

Controlled trial of Hartmann's solution versus 0.9% saline for diabetic ketoacidosis.

AIM: We aimed to determine whether using a balanced salt solution, Hartmann's solution (HS), in diabetic ketoacidosis (DKA) shortens the time to normalise acid-base status through the avoidance of hyperchloremic metabolic acidosis compared with 0.9% normal saline (NS). METHODS: We conducted a double-blind, randomised controlled trial comparing HS to NS as the initial intravenous fluid in children with DKA. Patients were stratified by severity (pH < 7.1) and known or new diabetes. Electrolytes, venous blood gases and glucose were measured every 2 h until intravenous fluids were ceased. The primary outcome was the time for the plasma bicarbonate to reach 15 mmol/L. Secondary outcomes included time to normalise pH (7.3), time to receive subcutaneous (SC) insulin, change in sodium and insulin requirement. RESULTS: A total of 77 children were enrolled. The groups were similar at baseline. There was no difference in the time to reach a bicarbonate of 15 mmol/L: geometric mean (SD) 8.6 (2.3) h for NS versus 6.2 (4.7) h for HS, ratio 1.4 (95% confidence interval 0.8-2.5), and no difference in time to normalise pH: NS 8.5 (2.3) h versus HS group 7.5 (1.8) h, ratio 1.1 (0.8-1.6). Kaplan-Meier survival estimates showed shorter times for these end-points in the severe subgroup: log-rank test P = 0.0277 and 0.0024, respectively. There was no difference in time to SC insulin, NS: 15.2 (2.4) h versus HS 14.3 (1.6) h, ratio 1.1 (0.8-1.5). Patients treated with HS received significantly less total fluids/kg. CONCLUSIONS: HS is an acceptable alternative to NS in DKA and may benefit those with severe DKA.

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.

Role of routine repeat head imaging in paediatric traumatic brain injury.

BACKGROUND: Paediatric traumatic brain injuries (TBI) remain a leading cause of morbidity and mortality in Australia. There are clear guidelines on head imaging for children with TBI, but there is conflicting evidence on the role of routine repeat head computed tomography (CT) scan. This study aims to determine whether routine repeat head CT scans in paediatric TBI alter surgical or medical management. METHODS: A retrospective study was performed at a level 1 tertiary paediatric trauma centre between January 2002 and July 2012. Patients with TBI who were admitted with acute intracranial injury and at least one repeat head CT scan were included. Mechanism of injury, severity of TBI, Glasgow Coma Score, use of intracranial pressure monitoring and operative procedures were listed. The need for operative management was compared for routine and clinically indicated head scans. RESULTS: Routine head CT scan was done in 36 out of 71 patients (51%). None from this group required craniotomy, but two children (6%) needed delayed ICP monitoring. Three patients with moderate to severe TBI required intracranial pressure monitor or external ventricular drain insertion based on a clinically indicated repeat head CT. CONCLUSION: Repeat head imaging is more likely to alter management of children with moderate to severe TBI. There is no role for routine repeat CT scan on mild TBI. Results of repeat cranial imaging should be correlated with the clinical status of the patient.

A multinational study of thromboprophylaxis practice in critically ill children.

OBJECTIVES: Although critically ill children are at increased risk for developing deep venous thrombosis, there are few pediatric studies establishing the prevalence of thrombosis or the efficacy of thromboprophylaxis. We tested the hypothesis that thromboprophylaxis is infrequently used in critically ill children even for those in whom it is indicated. DESIGN: Prospective multinational cross-sectional study over four study dates in 2012. SETTING: Fifty-nine PICUs in Australia, Canada, New Zealand, Portugal, Singapore, Spain, and the United States. PATIENTS: All patients less than 18 years old in the PICU during the study dates and times were included in the study, unless the patients were 1) boarding in the unit waiting for a bed outside the PICU or 2) receiving therapeutic anticoagulation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 2,484 children in the study, 2,159 (86.9%) had greater than or equal to 1 risk factor for thrombosis. Only 308 children (12.4%) were receiving pharmacologic thromboprophylaxis (e.g., aspirin, low-molecular-weight heparin, or unfractionated heparin). Of 430 children indicated to receive pharmacologic thromboprophylaxis based on consensus recommendations, only 149 (34.7%) were receiving it. Mechanical thromboprophylaxis was used in 156 of 655 children (23.8%) 8 years old or older, the youngest age for that device. Using nonlinear mixed effects model, presence of cyanotic congenital heart disease (odds ratio, 7.35; p < 0.001) and spinal cord injury (odds ratio, 8.85; p = 0.008) strongly predicted the use of pharmacologic and mechanical thromboprophylaxis, respectively. CONCLUSIONS: Thromboprophylaxis is infrequently used in critically ill children. This is true even for children at high risk of thrombosis where consensus guidelines recommend pharmacologic thromboprophylaxis.

Energy-efficient neuron, synapse and STDP integrated circuits.

Ultra-low energy biologically-inspired neuron and synapse integrated circuits are presented. The synapse includes a spike timing dependent plasticity (STDP) learning rule circuit. These circuits have been designed, fabricated and tested using a 90 nm CMOS process. Experimental measurements demonstrate proper operation. The neuron and the synapse with STDP circuits have an energy consumption of around 0.4 pJ per spike and synaptic operation respectively.

Pandemic H1N1 in children requiring intensive care in Australia and New Zealand during winter 2009.

OBJECTIVE: To describe in detail the pediatric intensive care experience of influenza A, particularly pandemic H1N1-09, in Australia and New Zealand during the 2009 Southern Hemisphere winter and to compare the pediatric experience with that of adults. METHOD: This was an inception-cohort study of all children who were admitted to intensive care with confirmed influenza A during winter 2009 at all general ICUs and PICUs in Australia and New Zealand. RESULTS: From June 1 through August 31, 2009, 107 children (20.0 per million [95% confidence interval: 16.1-23.8]) with influenza A, including 83 (15.5 per million [95% confidence interval: 12.1-18.9]) with H1N1-09 were admitted to ICUs. Fifty-two percent (39 of 75) of children with H1N1-09 had 1 or more comorbidity, most commonly neurologic (20%). Most (48 of 83 [58%]) presented with pneumonia. Thirteen of 83 (16%) had neurologic presentations. Eighty percent of the children with H1N1-09 required ventilation. Mortality was lower than in adults: 6 of 83 (7%) vs 114 of 668 (17%) (P = .02). The median length of stay for children with H1N1-09 was 5 days. Children with H1N1-09 occupied 773 bed-days (147 per million children) and 5.8% of specialist PICU beds. Presentation with septic shock or after cardiac arrest and the presence of 1 or more comorbidities were risk factors for severe disease. CONCLUSIONS: H1N1-09 caused a substantial burden on pediatric intensive care services in Australia and New Zealand. Compared with adults, children more commonly had nonrespiratory presentations and required ventilation more often but had a lower mortality rate.

Critical care services and 2009 H1N1 influenza in Australia and New Zealand.

BACKGROUND: Planning for the treatment of infection with the 2009 pandemic influenza A (H1N1) virus through health care systems in developed countries during winter in the Northern Hemisphere is hampered by a lack of information from similar health care systems. METHODS: We conducted an inception-cohort study in all Australian and New Zealand intensive care units (ICUs) during the winter of 2009 in the Southern Hemisphere. We calculated, per million inhabitants, the numbers of ICU admissions, bed-days, and days of mechanical ventilation due to infection with the 2009 H1N1 virus. We collected data on demographic and clinical characteristics of the patients and on treatments and outcomes. RESULTS: From June 1 through August 31, 2009, a total of 722 patients with confirmed infection with the 2009 H1N1 virus (28.7 cases per million inhabitants; 95% confidence interval [CI], 26.5 to 30.8) were admitted to an ICU in Australia or New Zealand. Of the 722 patients, 669 (92.7%) were under 65 years of age and 66 (9.1%) were pregnant women; of the 601 adults for whom data were available, 172 (28.6%) had a body-mass index (the weight in kilograms divided by the square of the height in meters) greater than 35. Patients infected with the 2009 H1N1 virus were in the ICU for a total of 8815 bed-days (350 per million inhabitants). The median duration of treatment in the ICU was 7.0 days (interquartile range, 2.7 to 13.4); 456 of 706 patients (64.6%) with available data underwent mechanical ventilation for a median of 8 days (interquartile range, 4 to 16). The maximum daily occupancy of the ICU was 7.4 beds (95% CI, 6.3 to 8.5) per million inhabitants. As of September 7, 2009, a total of 103 of the 722 patients (14.3%; 95% CI, 11.7 to 16.9) had died, and 114 (15.8%) remained in the hospital. CONCLUSIONS: The 2009 H1N1 virus had a substantial effect on ICUs during the winter in Australia and New Zealand. Our data can assist planning for the treatment of patients during the winter in the Northern Hemisphere.

Hyperchloraemic metabolic acidosis slows recovery in children with diabetic ketoacidosis: a retrospective audit.

INTRODUCTION: Hyperchloraemic metabolic acidosis (HMA) can occur in diabetic ketoacidosis (DKA), from urinary loss of bicarbonate precursors as ketones, or iatrogenically from chloride administration. OBJECTIVE: To determine whether children with DKA given normal saline developed HMA, and whether HMA delayed their recovery. SETTING: 13 Bed combined Paediatric Intensive Care/High Dependency Unit. METHODS: Retrospective analysis of the venous biochemistry of 59 admissions with DKA, recording the times to recovery from acidosis and normalisation of anion gap, and total intravenous chloride load. RESULTS: Twenty-nine (49%) were newly diagnosed diabetics. The median age was 12 (interquartile range, IQR 8.2-15.4) years. The initial pH in 23 (39%) was <7.1. The median times to achieve pH>7.3, bicarbonate>15mmol/l and anion gap<16.1 were 14.2h (IQR 8.6-20.1), 12.9h (IQR 8.6-20.0) and 10.7h (IQR 8.2-15.0) respectively. For individual patients, the median difference between recovery times for bicarbonate and anion gap was 0.18h (IQR 0-5.3), p=0.0005. However, in 14 patients (24%), the difference was >6h. These patients did not differ significantly in age or initial pH but had a lower initial bicarbonate (median 5 versus 7.8mmol/l, p=0.002), narrower anion gap (median 29.5 versus 31.6mmol/l, p=0.038), and took longer to normalise the bicarbonate: median 26.1 versus 10.5h, p<0.0001. They tended to be newly diagnosed presentations. CONCLUSION: The anion gap (AG) normalises earlier than bicarbonate in children with DKA treated with normal saline, and children with persisting HMA recover from acidosis more slowly.

Randomised controlled trial of intravenous maintenance fluids.

AIM: Traditional paediatric intravenous maintenance fluids are prescribed using hypotonic fluids and the weight-based 4:2:1 formula for administration rate. However, this may cause hyponatraemia in sick and post-operative children. We studied the effect of two types of intravenous maintenance fluid and two administration rates on plasma sodium concentration in intensive care patients. METHODS: A Factorial-design, double-blind, randomised controlled trial was used. We randomised 50 children with normal electrolytes without hypoglycaemia who needed intravenous maintenance fluids for >12 h to 0.9% saline (normal saline) or 4% dextrose and 0.18% saline (dextrose saline), at either the traditional maintenance fluid rate or 2/3 of that rate. The main outcome measure was change in plasma sodium from admission to 12-24 h later. RESULTS: Fifty patients (37 surgical) were enrolled. Plasma sodium fell in all groups: mean fall 2.3 (standard deviation 4.0) mmol/L. Fluid type (P = 0.0063) but not rate (P = 0.12) was significantly associated with fall in plasma sodium. Dextrose saline produced a greater fall in plasma sodium than normal saline: difference 3.0, 95% confidence interval 0.8-5.1 mmol/L. Full maintenance rate produced a greater fall in plasma sodium than restricted rate, but the difference was small and non-significant: 1.6 (-0.7, 3.9) mmol/L. Fluid type, but not rate, remained significant after adjustment for surgical status. One patient, receiving normal saline at restricted rate, developed asymptomatic hypoglycaemia. CONCLUSION: Sick and post-operative children given dextrose saline at traditional maintenance rates are at risk of hyponatraemia.

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.