Decreases in Nephrotoxic Pain Medications Are Not Associated With Increased Opioid Utilization in Critically Ill Children.

OBJECTIVES: Quality improvement initiatives to decrease rates of nephrotoxic medication exposure have reduced rates of acute kidney injury (AKI) in noncritically ill children. The objective of our study was to analyze the implementation of a similar program in critically ill children and to measure important balancing measures including opioid and benzodiazepine exposure. DESIGN: Prospective quality improvement study. SETTING: PICU at Children's Hospital Colorado between 2018 and 2020. PATIENTS: All children admitted to PICU. INTERVENTIONS: Quality improvement initiative called Nephrotoxic Injury Negated by Just-In-Time Action (NINJA). MEASUREMENT AND MAIN RESULTS: Eight thousand eight hundred thirty-three PICU patient admissions were included. Mean rates of nephrotoxic medication exposure/1,000 PICU patient days decreased from 46 to 26, whereas rates of nephrotoxic AKI/1,000 PICU patient days did not change. Nonsteroidal anti-inflammatory drug dispenses per 1,000 patient days were reduced from 521 to 456. Similarly, opioid and benzodiazepine exposures per 1,000 patient days were reduced from 812 to 524 and 441 to 227, respectively, during the study observation period. CONCLUSIONS: The NINJA intervention was efficaciously implemented in our single-center PICU. Nephrotoxic exposure is a modifiable factor that did not inadvertently increase exposure to opioids and benzodiazepines.

Concentrated hypertonic saline in severe pediatric traumatic brain injury.

OBJECTIVE: Describe outcomes associated with bolus and continuous infusions of hypertonic saline (HTS) in children with severe traumatic brain injury (TBI). METHODS: IRB-approved, single-center, retrospective review of children admitted between January 1, 2012 to August 30, 2018 with a diagnosis of severe TBI who received HTS. RESULTS: Forty-five children (age 9.3 ± 5.8 yr; 60% male) met inclusion criteria. One-hundred eighty-nine equiosmolar bolus doses of HTS were administered to 43 patients (3% HTS, n = 84 doses; 6% HTS, n = 38 doses; 12% HTS, n = 67 doses) for episodes of acute intracranial hypertension (pressure above 20 mmHg). Significant reductions in ICP were observed at 30, 60, and 120 min following HTS boluses with the greatest decrease observed in patients receiving 12%. Thirty-four patients received a continuous infusion of HTS. Higher concentrations of HTS were associated with a more favorable fluid balance (p < .001), fewer episodes of pulmonary edema (p = .003), and higher intake of protein and energy (p < .001). CONCLUSIONS: Equiosmolar bolus doses of concentrated HTS were associated with significant reductions in ICP. Benefits of higher concentrations of continuous HTS may include improved fluid balance, less pulmonary edema, and greater amounts of protein and energy intake.

Pediatric empyemas - Has the pendulum swung too far?

BACKGROUND: The management of childhood empyemas has transformed over the past decade, with current trends favoring chest tube placement and intrapleural fibrinolytic therapy. Although this strategy often avoids the need for video-assisted thoracoscopic surgery (VATS), hospital length of stay can be long. METHODS: To characterize national trends and outcomes associated with empyema management, the Pediatric Health Information System (PHIS) database was queried to identify children (2 months-18 years) treated for an empyema between January 2010 and December 2017. The cohort was divided into those treated with primary VATS and those treated with chest tube and intrapleural fibrinolysis. Number of chest radiographic studies obtained, frequency of pediatric intensive care unit (PICU) admission, mechanical ventilation requirements, and length of hospitalization were compared between groups. RESULTS: A total of 3,365 otherwise healthy children met inclusion criteria. Among them, 523 (16%) were managed with primary VATS and 2,842 (84%) were managed with chest tube and fibrinolytic therapy. Of those who were treated with chest tube and fibrinolysis, 193 (6.8%) subsequently underwent VATS. The percentage of children treated with chest tube and fibrinolysis increased from 65% in 2010 to 95% in 2017 (p<0.001). After adjusting for age, race, ethnicity, payer, and region, children who underwent primary VATS received fewer chest radiographic studies, were less likely to be admitted to the PICU or require mechanical ventilation and had a shorter PICU and hospital length of stay compared to those who were treated with chest tube and fibrinolytic therapy (p<0.001 for all analyses). DISCUSSION: Although national trends favor chest tube and fibrinolysis, primary VATS are associated with a shorter hospital and PICU length of stay and a lower requirement for mechanical ventilation. Future studies should aim to risk stratify children who may suffer from a protracted course with the goal to offer primary VATS to this subset of children and return them to normal life more expeditiously. LEVEL OF EVIDENCE: III.

Parallel assessment of CpG methylation by two-color hybridization with oligonucleotide arrays.

We have developed a method for the parallel analysis of multiple CpG sites in genomic DNA for their state of methylation. Hypermethylation of CpG islands within the promoters and 5' exons of genes has been found to be a mechanism of transcriptional inactivation associated with a variety of tumors. The method that we developed relies on the differential reactivity of methylated and unmethylated cytosines with sodium bisulfite, which exclusively converts unmethylated cytosines to deoxyuracils. The resulting sequence changes are determined with single-nucleotide resolution by hybridization to an oligonucleotide array. Cohybridization with a reference sample containing a different label provides an internal standard for assessment of methylation state. This method provides advantages in parallelism over existing methods of methylation analysis. We have demonstrated this technique with a region from the promoter of the tumor suppressor gene p16, which is hypermethylated in many cancers.