Alexandra Oschman

The survival of preterm infants continues to improve, along with an increased in neonatal intensive care unit (NICU) management of chronic infants who are medically complex infants who have prolonged hospital stays, sometimes up until 2 years of age. Despite advances in neonatal and infant care, the management of pain and sedation in chronic NICU patients continues to be a challenge. Challenges such as development of appropriate pain, sedation, and withdrawal scales along with unfamiliarity of the NICU care team with pediatric disease states and pharmacotherapy complicate management of these patients. Opioid induced hyperalgesia (OIH) and delirium may play a large role in these refractory cases, yet are often not considered in the NICU population. Drug therapy interventions such as gabapentin, ketamine, risperidone, and others have limited data for safety and efficacy in this population. This article summarizes the available literature regarding the evidence for diagnosis and management of infants with refractory pain and sedation along with the challenges that clinicians face when managing these patients.

OBJECTIVES: The objective of this multicenter survey is to characterize the use of direct thrombin inhibitors (DTIs) in the pediatric population. The results of this survey may be used to design a prospective multicenter study with the ultimate goal of developing a dosing/titration recommendation for the use of DTIs in the pediatric population. METHODS: This is a multicenter, descriptive study to survey hospitals around the country regarding the use of DTIs (argatroban, bivalirudin, and lepirudin) in the pediatic population. Institutional review board approval was obtained. The survey consisted of 42 questions and was designed utilizing Survey Monkey. The survey was emailed to members of the Pediatric Pharmacy Advocacy Group. Listserv members who responded to the survey within 4 weeks of when the survey was emailed were included in the study. Descriptive statistics were performed utilizing Microsoft Excel 2007. RESULTS: Responses were obtained from 56 institutions from 29 states in the United States. Multiple agents are available on formulary with argatroban being the most common (~80%). The large majority of institutions (41.1%) utilize DTIs 2 to 4 times a year with an additional 33.9% utilizing them less than twice a year. There is no consistent approach to dosing and titration amongst pediatric institutions. CONCLUSIONS: There are a wide variety of methods used by pediatric institutions with regard to dosing and titration of DTIs. Recently published prospective studies and package insert updates should help guide practitioners toward a more consistent approach to dosing of these high-risk medications.

Background: Thromboembolic events are occurring at increasing rates in neonates and infants. At Children's Mercy Hospitals and Clinics, antithrombin III (AT3) concentrates are often used in combination with enoxaparin to supplement physiologically low AT3 levels. Theoretically, AT3 enhances the anticoagulant activity of enoxaparin and results in decreased time to therapeutic anti‐Xa levels. No data exist on use of AT3 for this indication.Procedure: This retrospective study compared time to therapeutic anti‐Xa levels in patients P = 0.28). Initial enoxaparin dose and number of dose changes were equivalent. Group 1 required higher doses of enoxaparin to achieve therapeutic anti‐Xa levels. Age, critical illness, and timing of AT3 had no effect on time to therapeutic anti‐Xa levels. Bleeding events were not equivalent between Groups 1 and 2 (14.3% vs. 3.9%; P = 0.55).Conclusion: Supplementation with AT3 did not decrease time to therapeutic anti‐Xa levels, added significant cost, and was associated with increased bleeding events. Pediatr Blood Cancer 2014;61:1063–1067.

Congenital cytomegalovirus (CMV) infection is a major cause of birth defects and childhood disorders in the United States. Retinitis occurs in 25% of infants with severely symptomatic congenital CMV and in ∼1% of asymptomatic infants. Intravitreal ganciclovir is recommended in adults with CMV retinitis (CMVR) refractory or noncompliant to intravenous therapy. No literature is available discussing the use of intravitreal ganciclovir for CMVR in neonates. We report a term neonate who received intravenous and intravitreal ganciclovir for treatment of CMVR. Three doses of intravitreal ganciclovir (2 mg per dose in each eye) were administered. Intravitreal injections of ganciclovir appeared to be well tolerated and improvement of the retinitis was appreciated. Intravitreal ganciclovir is an effective treatment of CMVR in adult acquired immunodeficiency syndrome (AIDS) patients. We report one case of intravitreal ganciclovir in a term neonate with promising results.

Background:: A consensus has not been established for the standard treatment of hyperkalemia in the neonatal population. Most treatment regimens include a dextrose/insulin infusion. Additional agents used include calcium, sodium bicarbonate, polystyrene sulfonate, and albuterol. This study assessed the safety and efficacy of a potassium cocktail (k-cocktail) containing dextrose, insulin, calcium gluconate, and sodium lactate for treatment of neonatal hyperkalemia. Objective: To determine whether modifications to a potassium cocktail formulation, based on a prior quality improvement project, resulted in a decrease in the incidence of hyperglycemia and acidosis associated with its use, and to evaluate the effectiveness of the k-cocktail in lowering serum potassium levels and the incidence of adverse effects. Methods: We conducted a retrospective cohort study of neonates with hyperkalemia who received 2 k-cocktail formulations (group 1 [n = 13], original formulation, dextrose:insulin 5:1; group 2 [n = 26], modified formulation, dextrose: insulin 3.3:1). Group 2 subjects were matched 2:1 by gestational age and birth weight with those in group 1. Variables related to safety and effectiveness of therapy were assessed by medical record review. The following tests were used to assess group differences: χ ² , Fisher exact, 2-tailed t-tests, and mixed linear models. Results: The incidence of hyperglycemia during the modified k-cocktail infusion in group 2 decreased from 76.9% to 217% (p = 0.001). Serum blood glucose concentrations increased during the infusion, on average, for group 1 infants and were unchanged during the infusion for those in group 2. The incidence of acidosis during the infusion was similar between groups (group 1 [76.9%] vs group 2 [68.2%]; p = 0.58). No significant adverse events were observed. Serum potassium concentrations decreased similarly in both groups. Conclusions: An intravenous infusion including a dextrose:insulin ratio of 3.3:1. compared with a higher ratio, results in less hyperglycemia and appears to be as effective in decreasing potassium concentrations in newborns.

Purpose The published literature on the use of dexmedetomidine as an adjunct to sedation and analgesia in the management of pediatric narcotic withdrawal was reviewed. Summary Pediatric narcotic withdrawal syndromes are reported to be increasingly frequent in pediatric intensive care units. A number of tools specifically designed for assessment of withdrawal in newborns and infants are in current use, including the widely used Finnegan Scoring System. A limited number of studies and case reports suggest that dexmedetomidine, an α₂-receptor agonist with a mechanism of action similar to that of clonidine but with greater α₂-receptor specificity, might have a role in the treatment of pediatric withdrawal (by blunting withdrawal symptoms without causing respiratory depression and by permitting shorter narcotic tapering schedules) and also in the prevention of pediatric narcotic withdrawal (by reducing narcotic requirements). Potential adverse effects associated with dexmedetomidine use in pediatric patients are generally associated with use of bolus doses and mainly involve central nervous system effects (e.g., hypotension, bradycardia), with no hemodynamic manifestations. When bolus doses are used, strategies described in published reports entail a loading dose of 0.5–1.0 μg/kg administered over 5–10 minutes, followed by a continuous infusion at 0.1–1.4 μg/kg/hr for a period of 1–16 days. More research is needed to define the optimal use of dexmedetomidine in the management of pediatric narcotic withdrawal. Conclusion A limited body of published evidence from retrospective studies and case reports suggests a potential role for dexmedetomidine as an adjunct therapy to provide sedation and analgesia to reduce narcotic withdrawal symptoms in pediatric patients.