Management of Sleep Disorders in Children With Neurodevelopmental Disorders: A Review.

Neurodevelopmental disorders (NDDs) are defined as a group of disorders caused by changes in early brain development, resulting in behavioral and cognitive alterations in sensory and motor systems, speech, and language. NDDs affect approximately 1-2% of the general population. Up to 80% of children with NDDs are reported to have disrupted sleep; subsequent deleterious effects on daytime behaviors, cognition, growth, and overall development of the child are commonly reported. Examples of NDDs discussed in this review include autism spectrum disorder, cerebral palsy, Rett syndrome, Angelman syndrome, Williams syndrome, and Smith-Magenis syndrome. The etiology of sleep disorders in children with NDDs is largely heterogeneous and disease specific. The diagnosis and management of sleep disorders in this population are complex, and little high-quality data exist to guide a consistent approach to therapy. Managing sleep disorders in children with NDDs is critical both for the child and for the family but is often frustrating due to the refractory nature of the problem. Sleep hygiene must be implemented as first-line therapy; if sleep hygiene alone fails, it should be combined with pharmacologic management. The available evidence for the use of common pharmacologic interventions, such as iron supplementation and melatonin, as well as less common interventions, such as melatonin receptor agonists, clonidine, gabapentin, hypnotics, trazodone, and atypical antipsychotics is reviewed. Further, parents and caregivers should be provided with appropriate education on the nature of the sleep disorders and the expectation for modest pharmacologic benefit, at best. Additional data from well-designed trials in children with NDDs are desperately needed to gain a better understanding of sleep pharmacotherapy including efficacy and safety implications. Until then, clinicians must rely on the limited available data, as well as clinical expertise, when managing sleep disorders in the population of children with NDDs.

Three-in-one parenteral nutrition in neonates and pediatric patients: risks and benefits.

Parenteral nutrition (PN) is a life-sustaining therapy designed to deliver essential nutrients to patients unable to meet nutrition needs via the enteral route. PN may be delivered via a 2-in-1 system (one solution containing amino acids, dextrose, electrolytes, vitamins, minerals, and fluids and one solution containing intravenous fat emulsions [IVFEs]) or via a 3-in-1 system (all nutrients mixed in one container). Although the use of 3-in-1 PN solutions is not necessarily therapeutically advantageous, certain benefits may exist such as the potential to reduce the risk of contamination due to decreased manipulations; ease of administration, particularly in the home care setting; possible cost savings; and reduced IVFE wastage. However, the incorporation of IVFE in 3-in-1 solutions also presents unique risks for the neonatal and pediatric population such as decreased stability, increased lipid globule size, decreased sterility and the potential for increased microbial growth/infectious complications, the need to use a larger filter size, precipitation and compatibility risks, and an increased chance of catheter occlusion. This review outlines the unique issues and challenges to be considered when formulating neonatal and pediatric 3-in-1 PN admixtures. While 3-in-1 PN solutions may be advantageous for certain pediatric populations, specifically those dependent on home PN, the risks do not outweigh the benefits in neonatal patients, and use should be avoided in this population.

Infectious complications with nondaily versus daily infusion of intravenous fat emulsions in non-critically ill adults.

BACKGROUND: Increased risk for infection has been associated with the administration of intravenous fat emulsion (IVFE). Typically, IVFE is infused daily as part of the parenteral nutrition (PN) regimen. However, a national IVFE shortage in 2010 compelled institutions to restrict administration to nondaily. This retrospective study evaluated the rate of infections associated with the nondaily as compared to daily IVFE infusion in hospitalized adult patients. METHODS: Patients in the study group received nondaily IVFE during the shortage period, and patients in the control group received daily IVFE. The primary outcomes were the development of catheter-related bloodstream infections (CR-BSIs) or any bloodstream infection (BSI). Secondary outcomes were the development of respiratory, urinary, wound, or other infections. RESULTS: Included in the study were 52 patients, 33 patients in the study group and 19 patients in the control group. There were no CR-BSIs reported. BSIs occurred in 1 patient in the study group. The total number of infections and urinary tract infections (UTIs) per 1000 catheter days were not different between the 2 groups (45.28 vs 21.24, P = .203) and (24.39 vs 5.525, P = .099), respectively. Survival analyses showed no difference between the 2 groups for the time to first infection (11.24 vs 6.59 days, P = .30) and time to first UTI (11.97 vs 7 days, P = .093), respectively. CONCLUSIONS: Nondaily vs daily IVFE infusion did not have a significant effect on the risk of infection or time to development of infection; however, results are limited due to the small sample size. Large prospective randomized clinical trials are needed to further evaluate the effect of daily as compared to nondaily IVFE infusion on infectious complications.

Management of copper deficiency in cholestatic infants: review of the literature and a case series.

Copper is an essential trace element, playing a critical role in multiple functions in the body. Despite the necessity of adequate copper provision and data supporting the safety of copper administration during cholestasis, it remains common practice to reduce or remove copper in parenteral nutrition (PN) solutions after the development of cholestasis due to historical recommendations supporting this practice. In neonates, specifically premature infants, less is known about required copper intakes to accumulate copper stores and meet increased demands during rapid growth. Pediatric surgical patients are at high risk for hepatic injury during long-term PN provision and a balance is needed between the potential for reduced biliary excretion of copper and adequate copper intakes to prevent deficiency. Copper deficiency has been documented in several pediatric patients with cholestasis when parenteral copper was reduced or removed. Few data guide the management of copper deficiency in the pediatric population. The following case series describes our experience with successfully managing copper deficiency in 3 cholestatic infants after copper had been reduced or removed from their PN. Classic signs of copper deficiency were present, including hypocupremia, anemia, neutropenia, thrombocytopenia, and osteopenia. Treatment included use of both parenteral and enteral copper supplementation. We suggest revision of current recommendations regarding decreasing copper in PN during cholestasis with a proposed algorithm for parenteral copper provision in the setting of cholestasis that is based on evaluation of measured serum copper concentrations.

Fondaparinux and the management of heparin-induced thrombocytopenia: the journey continues.

OBJECTIVE: To review the available literature addressing the role of fondaparinux in the management of heparin-induced thrombocytopenia (HIT). DATA SOURCES: Primary articles were identified by a MEDLINE search (2004-June 2009) of English-language literature using the MeSH headings fondaparinux, heparin, low-molecular-weight heparin, and thrombocytopenia. Relevant consensus guidelines (2006-June 2009) were also identified. STUDY SELECTION AND DATA EXTRACTION: All published studies and case reports, as well as relevant consensus guidelines, evaluating the use of fondaparinux for the management of HIT were included. DATA SYNTHESIS: The role of fondaparinux in the management of HIT is a therapeutic controversy challenging clinicians today. An open-label, prospective pilot study of 7 patients with acute HIT supports fondaparinux as an alternative anticoagulant. Additionally, a total of 12 patients with HIT from a larger case study and retrospective cohort were successfully treated with fondaparinux. Much of the supporting data exists in the form of case reports, each demonstrating normalization of platelet counts without any evidence of new thrombosis. The differences in clinical scenarios as well as the role and dose of fondaparinux make interpretation of these reports difficult. Three case reports have been published raising concerns regarding fondaparinux causing or failing to manage HIT appropriately. However, common weaknesses such as small sample sizes and nonuniform definitions of HIT limit the usefulness of these findings. The updated American College of Chest Physicians consensus guidelines now recognize fondaparinux as an option in the management of HIT; however, the level of evidence supporting this is of low quality. The use of fondaparinux as a bridging agent between direct thrombin inhibitor and warfarin therapy has been proposed. A recently published case report gives support to this approach. CONCLUSIONS: Controlled clinical trials evaluating the use of fondaparinux in the management of HIT need to be completed before this therapy can be routinely recommended.