Pragmatic Randomized Trial of Corticosteroids and Inhaled Epinephrine for Bronchiolitis in Children in Intensive Care.

OBJECTIVE: To determine whether the combination of systemic corticosteroids and nebulized epinephrine, compared with standard care, reduces the duration of positive pressure support in children with bronchiolitis admitted to intensive care. STUDY DESIGN: We performed a pragmatic, multicenter, open-label, randomized trial between July 2013 and November 2019 in children younger than 18 months old with a clinical diagnosis of bronchiolitis. The intervention group received the equivalent of 13 mg/kg prednisolone over 3 days, then 1 mg/kg daily for 3 days, plus 0.05 mL/kg of nebulized 1% epinephrine made up to 6 ml with 0.9% saline via jet nebulizer and mask using oxygen at 12 l/min every 30 minutes for 5 doses, then 1-4 hourly for 3 days, then as required for 3 days. The primary outcome was clinician-managed duration of positive pressure support in intensive care defined as high-flow nasal-prong oxygen, nasopharyngeal continuous positive airway pressure, or mechanical ventilation. RESULTS: In total, 210 children received positive pressure support. In the corticosteroid-epinephrine group, 107 children received positive pressure support for a geometric mean of 26 (95% CI, 22-32) hours compared with 40 (95% CI 34-47) hours in 103 controls, adjusted ratio 0.66 (95% CI 0.51-0.84), P = .001. In the intervention group, 41 (38%) children experienced at least 1 adverse event, compared with 39 (38%) in the control group. CONCLUSIONS: In children with severe bronchiolitis, the duration of clinician-managed pressure support was reduced by regular treatment with systemic corticosteroids and inhaled epinephrine compared with standard care. CLINICAL TRIAL REGISTRATION: Australian Clinical Trials Research Network: ACTRN12613000316707.

Identifying Children at Risk of Malignant Bordetella pertussis Infection.

OBJECTIVE: To identify factors associated with malignant pertussis. DESIGN: A retrospective case notes review from January 2003 to August 2013. Area under the receiver-operator characteristic curve was used to determine how well vital sign and white cell characteristics within 48 hours of hospital presentation identified children with malignant pertussis. SETTING: The national children's hospital in Auckland, New Zealand. PATIENTS: One hundred fifty-two children with pertussis. MEASUREMENTS AND MAIN RESULTS: There were 152 children with confirmed pertussis identified, including 11 children with malignant pertussis. The area under the receiver-operator characteristic curve was 0.88 (95% CI, 0.78-0.97) for maximum heart rate. The optimal cut-point was 180 beats/min, which predicted malignant pertussis with a sensitivity of 73% and a specificity of 91%. The area under the receiver-operator characteristic curve was 0.92 (95% CI, 0.81-1.0) for absolute neutrophil count, 0.85 (95% CI, 0.71-0.99) for total WBC count, 0.80 (95% CI, 0.63-0.96) for neutrophil-to-lymphocyte ratio, and 0.77 (95% CI, 0.58-0.92) for absolute lymphocyte count. All children with malignant pertussis had one or more of heart rate greater than 180 beats/min, total WBC count greater than 25 × 10/L, and neutrophil-to-lymphocyte ratio greater than 1.0 with an area under the receiver-operator characteristic curve of 0.96 (95% CI, 0.91-1.0) for a multivariate model that included these three variables. CONCLUSIONS: Clinical predictors of malignant pertussis are identifiable within 48 hours of hospital presentation. Early recognition of children at risk of malignant pertussis may facilitate early referral to a PICU for advanced life support and selection for trials of investigational therapies.

Impact of Retrieval, Distance Traveled, and Referral Center on Outcomes in Unplanned Admissions to a National PICU.

OBJECTIVES: Centralization of PICUs requires a transport system that delivers patient outcomes equivalent to that of the same institution admissions. Our aim was to evaluate how pediatric critical care retrieval, distance traveled, and referral center level of ICU support impact on outcomes in unplanned admissions. DESIGN: Retrospective cohort study. SETTING: The national PICU in New Zealand. PATIENTS: A total of 5,609 (45% retrieved) unplanned pediatric admissions (< 15 yr) between January 1, 2004, and January 1, 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data analyzed included case-mix, source of admission, diagnostic category, Pediatric Index of Mortality score, PICU-specific resource use, distance traveled, transport duration, and referral hospital ICU level. Outcome measures were crude and risk-adjusted PICU mortality and PICU length of stay. Compared with nontransported admissions, retrieved children were younger, more frequently admitted outside normal working hours, had higher predicted mortality (median Pediatric Index of Mortality score, 4.7% vs 1.5%; p < 0.001) and PICU-specific resource use (respiratory support, vasoactive infusions, and renal replacement therapy). The transport cohort had greater crude mortality rates (8.6% vs 5.6%; p < 0.008) and a median of 29 hours longer PICU stay. There was no significant difference in risk-adjusted mortality between the cohorts (observed/expected mortality ratio for retrieved patients, 0.84 vs nontransported patients, 0.91; p = 0.73). Neither distance traveled (median, 135 km), transport duration (median, 4.4 hr), nor the level of ICU at the referral center had a significant effect on risk-adjusted PICU mortality in the retrieved cohort. CONCLUSIONS: Children retrieved to the national PICU in New Zealand have greater predicted mortality risk and PICU-specific resource use than nontransported patients. There is no significant difference in risk-adjusted mortality between retrieved and the same institution admissions. Critically ill pediatric patients can be transported long distances by specially trained and equipped transport teams, without an increase in risk-adjusted PICU mortality.

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.

Varicella in a Paediatric Intensive Care Unit: 10-year review from Starship Children's Hospital, New Zealand.

AIMS: Varicella is now a vaccine-preventable disease but is generally considered benign, making it a low priority for a funded universal immunisation scheme. We aimed to increase the knowledge of the severity, morbidity and mortality caused by varicella, by a review of cases requiring paediatric intensive care in New Zealand where vaccine is available but not funded. METHODS: This is a retrospective chart review of children admitted to the paediatric intensive care unit (PICU) over a 10-year period (July 2001-July 2011) identified from the PICU database with a primary or secondary code for varicella. RESULTS: Thirty-four cases were identified and 26 cases were included. Of the 26 cases, 84.6% were Maori or Pacific Island ethnicity, 54% had no preceding medical condition and 23% were immunocompromised. Main PICU admission reasons were neurologic (38.5%), secondary bacterial sepsis or shock (26.9%), respiratory (15.4%), disseminated varicella (11.5%), or other causes (7.7%). Fifty per cent of children required inotropic support and 81% invasive ventilation. Four children died (15%), three of whom were immunocompromised. A further eight children (31%) had ongoing disability at hospital discharge. CONCLUSION: Varicella, or its secondary complications, requiring paediatric intensive care, carries high mortality, particularly for immunocompromised patients, and long-term morbidities, mostly affecting previously healthy children.

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.

Two Randomized Trials of the Effect of the Russian Strain of Bacillus Calmette-Guérin Alone or With Oral Polio Vaccine on Neonatal Mortality in Infants Weighing <2000 g in India.

BACKGROUND: In randomized trials in Guinea-Bissau, the Danish strain of Bacillus Calmette-Guérin (BCG) reduces neonatal mortality, primarily by reducing deaths from pneumonia and sepsis. Because World Health Organization-prequalified BCG-Denmark was not available in India, we conducted 2 randomized trials to test whether BCG-Russia alone or with oral polio vaccine (OPV) has similar effects to BCG-Denmark. METHODS: We randomized neonates weighing <2000 g to a control group that was not vaccinated before 28 days of age or to receive either BCG-Russia alone (first trial) or BCG-Russia with OPV (second trial) soon after birth. We performed intention-to-treat analysis using Cox hazards models with age as the underlying time and adjusted for weight, sex and inborn versus outborn status. RESULTS: Administration of BCG-Russia alone had no effect on neonatal mortality (to 28 days of age): 15.6% of 1537 infants died in the BCG-Russia group and 16.1% of 1535 died in the control group; the adjusted hazard ratio was 0.95 [95% confidence interval (CI): 0.80-1.13]. Administration of BCG-Russia with OPV also had no effect on neonatal mortality: 18.0% of 1103 infants died in the BCG-OPV group and 17.6% of 1104 died in the control group; the adjusted hazard ratio was 1.01 (95% CI: 0.83-1.23). The adjusted hazard ratio for the 2 trials combined was 0.98 (95% CI: 0.85-1.11). CONCLUSIONS: BCG-Russia with or without OPV had no effect on neonatal mortality. It is important to determine which strains of BCG have the greatest specific effects (on tuberculosis) and nonspecific effects (on infections other than tuberculosis) in high-mortality regions.

Increasing Incidence of Life-threatening Pertussis: A Retrospective Cohort Study in New Zealand.

BACKGROUND: Pertussis immunization programs aim to prevent severe infant disease. We investigated temporal trends in infant pertussis deaths and pediatric intensive care unit (PICU) admissions and associations of changes in disease detection and vaccines used with death and PICU admission rates. METHODS: Using national data from New Zealand (NZ), we described infant pertussis deaths and PICU admissions from 1991 to 2013, over which time national immunization coverage at 2 years of age increased from <80% to 92%. In NZ, pertussis became a notifiable disease with polymerase chain reaction (PCR) diagnosis available in 1997 and acellular replaced whole-cell vaccine in 2000. We used Poisson regression to model temporal trends and compared rates in time intervals using rate ratios (RRs) with 95% confidence intervals (CIs). RESULTS: There were 10 pertussis deaths and 159 infant PICU admissions with pertussis from 1991 to 2013. The annual number of infant pertussis PICU admissions increased from 1991 to 2013 (P = 0.02) but the number of pertussis deaths did not (P = 0.09). The risk of PICU admission during infancy with pertussis was increased in the notification/PCR versus the non-notification/PCR era (RR: 1.12; 95% CI: 1.02-1.19) and when acellular replaced whole-cell vaccine (RR: 1.19; 95% CI: 1.06-1.31). Median Pediatric Index of Mortality scores during 2001-2013 were lower than during 1991-1999 (P < 0.001). CONCLUSIONS: Infant PICU pertussis admission rates have increased in NZ despite improvements in immunization coverage. Higher rates have occurred since pertussis notification/PCR became available and since acellular replaced whole-cell vaccine. The severity of disease in infants admitted to PICU with pertussis has decreased in recent years.

Thrombocytopenia-associated multiorgan failure occurring in an infant at the onset of type 1 diabetes successfully treated with fresh frozen plasma.

TAMOF is a devastating microangiopathy that can occur in association with the new onset of T1DM, and should be considered with the onset of thrombocytopenia, renal failure, and raised LDH. Treatment with fresh frozen plasma should be considered as a first-line option in such cases prior to plasma exchange.