Acute Kidney Injury During Treatment with Intravenous Acyclovir for Suspected or Confirmed Neonatal Herpes Simplex Virus Infection.

OBJECTIVE: To describe the epidemiology of and risk factors associated with acute kidney injury (AKI) during acyclovir treatment in neonates and infants. STUDY DESIGN: We conducted a multicenter (n = 4), retrospective cohort study of all hospitalized infants age <60 days treated with intravenous acyclovir (≥1 dose) for suspected or confirmed neonatal herpes simplex virus disease from January 2011 to December 2015. Infants with serum creatinine measured both before acyclovir (baseline) and during treatment were included. We classified AKI based on changes in creatinine according to published neonatal AKI criteria and performed Cox regression analysis to evaluate risk factors for AKI during acyclovir treatment. RESULTS: We included 1017 infants. The majority received short courses of acyclovir (median, 5 doses). Fifty-seven infants (5.6%) developed AKI during acyclovir treatment, with an incidence rate of AKI at 11.6 per 1000 acyclovir days. Cox regression analysis identified having confirmed herpes simplex virus disease (OR, 4.35; P = .002), receipt of ≥2 concomitant nephrotoxic medications (OR, 3.07; P = .004), receipt of mechanical ventilation (OR, 5.97; P = .001), and admission to an intensive care unit (OR, 6.02; P = .006) as risk factors for AKI during acyclovir treatment. CONCLUSIONS: Among our cohort of infants exposed to acyclovir, the rate of AKI was low. Sicker infants and those exposed to additional nephrotoxic medications seem to be at greater risk for acyclovir-induced toxicity and warrant closer monitoring.

Lower-Dose, Intravenous Chlorothiazide Is an Effective Adjunct Diuretic to Furosemide Following Pediatric Cardiac Surgery.

OBJECTIVES: Postoperative fluid overload is ubiquitous in neonates and infants following operative intervention for congenital heart defects; ineffective diuresis is associated with poor outcomes. Diuresis with furosemide is widely used, yet there is often resistance at higher doses. In theory, furosemide resistance may be overcome with chlorothiazide; however, its efficacy is unclear, especially in lower doses and in this population. We hypothesized the addition of lower-dose, intravenous chlorothiazide following surgery in patients on high-dose furosemide would induce meaningful diuresis with minimal side effects. METHODS: This was a retrospective, cohort study. Postoperative infants younger than 6 months, receiving high-dose furosemide, and given lower-dose chlorothiazide (1-2 mg/kg every 6-12 hours) were identified. Diuretic doses, urine output, fluid balance, vasoactive-inotropic scores, total fluid intake, and electrolyte levels were recorded. RESULTS: There were 73 patients included. The addition of lower-dose chlorothiazide was associated with a significant increase in urine output (3.8 ± 0.18 vs 5.6 ± 0.27 mL/kg/hr, p < 0.001), more negative fluid balance (16.1 ± 4.2 vs -25.0 ± 6.3 mL/kg/day, p < 0.001), and marginal changes in electrolytes. Multivariate analysis was performed, demonstrating that increased urine output and more negative fluid balance were independently associated with addition of chlorothiazide. Subgroup analysis of 21 patients without a change in furosemide dose demonstrated the addition of chlorothiazide significantly increased urine output (p = 0.03) and reduced fluid balance (p < 0.01), further validating the adjunct effects of chlorothiazide. CONCLUSION: Lower-dose, intravenous chlorothiazide is an effective adjunct treatment in postoperative neonates and infants younger than 6 months following cardiothoracic surgery.

Safety, Efficacy, and Timeliness of Intravenous Potassium Chloride Replacement Protocols in a Pediatric Cardiothoracic Intensive Care Unit.

OBJECTIVE: Hypokalemia in children following cardiac surgery occurs frequently, placing them at risk of life-threatening arrhythmias. However, renal insufficiency after cardiopulmonary bypass warrants careful administration of potassium (K+). Two different nurse-driven protocols (high dose and tiered dosing) were implemented to identify an optimal K+ replacement regimen, compared to an historical low-dose protocol. Our objective was to evaluate the safety, efficacy, and timeliness of these protocols. DESIGN: A retrospective cohort review of pediatric patients placed on intravenous K+ replacement protocols over 1 year was used to determine efficacy and safety of the protocols. A prospective single-blinded review of K+ repletion was used to determine timeliness. PATIENTS: Pediatric patients with congenital or acquired cardiac disease. SETTING: Twenty-four-bed cardiothoracic intensive care unit in a tertiary children's hospital. INTERVENTIONS: Efficacy was defined as fewer supplemental potassium chloride (KCl) doses, as well as a higher protocol to total doses ratio per patient. Safety was defined as a lower percentage of serum K+ levels ≥4.8 mEq/L after a dose of KCl. Between-group differences were assessed by nonparametric univariate analysis. RESULTS: There were 138 patients with a median age of 3.0 (interquartile range: 0.23-10.0) months. The incidence of K+ levels ≥4.8 mEq/L after a protocol dose was higher in the high-dose protocol versus the tiered-dosing protocol but not different between the low-dose and tiered-dosing protocols (high dose = 2.2% vs tiered dosing = 0.5%, P = .05). The ratio of protocol doses to total doses per patient was lower in the low-dose protocol compared to the tiered-dosing protocol (P < .05). Protocol doses were administered 45 minutes faster (P < .001). CONCLUSION: The tiered-dosed, nurse-driven K+ replacement protocol was associated with decreased supplemental K+ doses without increased risk of hyperkalemia, administering doses faster than individually ordered doses; the protocol was effective, safe, and timely in the treatment of hypokalemia in pediatric patients after cardiac surgery.

Serious Adverse Events Associated with Off-Label Use of Azithromycin or Fentanyl in Children in Intensive Care Units: A Retrospective Chart Review.

OBJECTIVES: Half of prescription drugs commonly given to children lack product labeling on pediatric safety, efficacy, and dosing. Two drugs most widely used off-label in pediatrics are azithromycin and fentanyl. We sought to determine the risk of serious adverse events (SAEs) when oral azithromycin or intravenous/intramuscular fentanyl are used off-label compared to on-label in pediatric intensive care units (ICUs). STUDY DESIGN: Six pediatric hospitals participated in a retrospective chart review of patients administered oral azithromycin (n = 241) or intravenous/intramuscular fentanyl (n = 367) between January 5, 2013 and December 26, 2014. Outcomes were SAEs by drug and labeling status: off-label compared to on-label by Food and Drug Administration (FDA)-approved age and/or indication. Statistical analysis was performed using logistic regression to estimate odds ratios (ORs) and Cox regression to estimate hazard ratios (HRs). RESULTS: Twenty-one (9%) children receiving azithromycin experienced SAEs. Off-label use of azithromycin was not associated with a higher risk of SAE (OR 0.87, 95% CI 0.27-2.71, p = 0.81). Ninety-five (26%) children receiving fentanyl experienced SAEs. Fentanyl off-label use by both age and indication was not associated with a higher risk of overall SAEs compared to on-label use (OR 1.99, 95% CI 0.94-4.19, p = 0.07). However, the risk of the SAE respiratory depression was significantly greater when fentanyl was used off-label by both age and indication (OR 5.05, 95% CI 1.08-23.56, p = 0.044). Results based on HRs were similar. CONCLUSIONS: Azithromycin off-label use in pediatric ICUs does not appear to be associated with an increased risk of SAEs. Off-label use of fentanyl appears to be more frequently associated with respiratory depression when used off-label by both age and indication in pediatric ICUs. Prospective studies should be undertaken to assess the safety and efficacy of fentanyl in the pediatric population so that data can be added to the FDA labeling.

Implementation of a Risk-Stratified Opioid and Benzodiazepine Weaning Protocol in a Pediatric Cardiac ICU.

OBJECTIVES: Opioids and benzodiazepines are commonly used to provide analgesia and sedation for critically ill children with cardiac disease. These medications have been associated with adverse effects including delirium, dependence, withdrawal, bowel dysfunction, and potential neurodevelopmental abnormalities. Our objective was to implement a risk-stratified opioid and benzodiazepine weaning protocol to reduce the exposure to opioids and benzodiazepines in pediatric patients with cardiac disease. DESIGN: A prospective pre- and postinterventional study. PATIENTS: Critically ill patients less than or equal to 21 years old with acquired or congenital cardiac disease exposed to greater than or equal to 7 days of scheduled opioids ± scheduled benzodiazepines between January 2013 and February 2015. SETTING: A 24-bed pediatric cardiac ICU and 21-bed cardiovascular acute ward of an urban stand-alone children's hospital. INTERVENTION: We implemented an evidence-based opioid and benzodiazepine weaning protocol using educational and quality improvement methodology. MEASUREMENTS AND MAIN RESULTS: One-hundred nineteen critically ill children met the inclusion criteria (64 post intervention, 55 pre intervention). Demographics and risk factors did not differ between groups. Patients in the postintervention period had shorter duration of opioids (19.0 vs 30.0 d; p < 0.01) and duration of benzodiazepines (5.3 vs 22.7 d; p < 0.01). Despite the shorter duration of wean, there was a decrease in withdrawal occurrence (% Withdrawal Assessment Tool score ≥ 4, 4.9% vs 14.1%; p < 0.01). There was an 8-day reduction in hospital length of stay (34 vs 42 d; p < 0.01). There was a decrease in clonidine use (14% vs 32%; p = 0.02) and no change in dexmedetomidine exposure (59% vs 75%; p = 0.08) in the postintervention period. CONCLUSIONS: We implemented a risk-stratified opioid and benzodiazepine weaning protocol for critically ill cardiac children that resulted in reduction in opioid and benzodiazepine duration and dose exposure, a decrease in symptoms of withdrawal, and a reduction in hospital length of stay.

Implementation of a risk-stratified opioid weaning protocol in a pediatric intensive care unit.

PURPOSE: Opioids are important in the care of critically ill children. However, their use is associated with complications including delirium, dependence, withdrawal, and bowel dysfunction. Our aim was to implement a risk-stratified opioid weaning protocol to reduce the duration of opioids without increasing the incidence of withdrawal. METHODS: A pre- and post-interventional prospective study was undertaken in a large children's hospital pediatric ICU where we implemented a risk-stratified opioid weaning protocol. Patients were included if exposed to ≥7days of scheduled opioids. The primary outcome was duration of opioids and secondary outcome was hospital LOS. RESULTS: One hundred seven critically ill children met the inclusion criteria (68 pre-, 39 post-intervention). Demographics, risk factors, and confounders did not differ between groups. Patients in the post-intervention group had shorter duration of opioids (17 vs. 22.5days, p=0.01) and opioid wean (12 vs. 18days, p=0.01). Despite the shorter duration of opioid wean, there was no increase in withdrawal incidence. There was no difference in the LOS (29 vs. 33days, p=0.06). CONCLUSIONS: We implemented a risk-stratified opioid weaning protocol for critically ill children that resulted in reduction in opioid exposure without an increase in withdrawal. There was no difference in the LOS.