Immunosuppression Regimens for Intestinal Transplantation in Children.

Pediatric intestinal transplant serves as the only definitive treatment for children with irreversible intestinal failure. Successful intestinal transplant hinges upon appropriate management of immunosuppression. The indications for intestinal transplant have changed over time. Immunosuppression regimens can be divided into induction and maintenance phases along with treatment of acute rejection. Intestinal transplant induction now often includes antithymocyte globulin or basiliximab in addition to corticosteroids. Maintenance regimens continue to be dominated by tacrolimus, with additional agents used to either decrease goal tacrolimus levels to limit toxicity or as an adjunct in sensitized patients. Careful monitoring can help to limit serious complications, such as rejection, infection, and malignancy. Future work will aim to decrease variation in practice and identify methods to determine optimal immunosuppression for a particular patient. Furthermore, there is a need for non-invasive monitoring of the intestinal graft and functional assessments of immunosuppression.

Pharmacological management of portal hypertension and its complications in children: lessons from adults and opportunities for the future.

INTRODUCTION: Portal hypertension (PHT) and its complications in children are thought to be distinct from adult PHT in several areas, including the underlying bio-physiology of a child in which PHT develops, but also because of the pediatric-specific etiologies that drive disease progression. And yet pharmacologic approaches to PHT in children are mainly based on adult data, modified for pediatric practice. This reality has been driven by a lack of data specific to children. AREAS COVERED: The authors discuss current therapeutic approaches to PHT in children, including management of acute gastrointestinal variceal bleed, pharmacotherapy in prophylaxis, and established and emerging therapies to combat systemic co-morbidities that result from PHT. The few areas where pediatric-specific data exist are highlighted and the many gaps in knowledge that remain unresolved are underscored. EXPERT OPINION: Despite decades of experience, optimal management of pediatric PHT remains undefined. In large part, this can be directly linked to a lack of basic understanding related to the unique pathophysiology and natural history that defines PHT in children. As a result, meaningful research into the utility and effectiveness of pharmacotherapy in children with PHT remains in its infancy. Large, multi-center, prospective studies will be needed to begin to establish an infrastructure on which a pediatric-specific research agenda can be built.

Neurostimulant Prescribing Patterns in Children Admitted to the Intensive Care Unit after Traumatic Brain Injury.

Neurostimulant medications are commonly prescribed following traumatic brain injury (TBI) in adults; little is known about their use in children with TBI. Our objective was to analyze neurostimulant prescribing practices from 2005 to 2015 in children admitted to the intensive care unit (ICU) with TBI. We hypothesized that neurostimulant prescriptions have increased over time and are associated with older age and injury severity. A retrospective cohort study of patients age 1 month to 18 years with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) discharge diagnosis code for TBI admitted to the ICU between 2005 and 2015 in 37 pediatric hospitals included in the Pediatric Health Information System was conducted. Variables examined include patient and injury characteristics and neurostimulant medication use. Descriptive statistics and multi-variable logistic regression testing were used to determine variables associated with neurostimulant prescription. Of 30,881 patients with TBI, most were male (64%) and age 0-4 years (43%). In patients with mechanism of injury reported (n = 21,998), TBI was most frequently due to falls (36%) and motor vehicle collisions (36%). One thousand sixty-four neurostimulants were prescribed to 878 (3%) patients with 41% of prescriptions for amantadine and 38% for methylphenidate. Neurostimulants were prescribed a median (interquartile range) of 17 (8-35) days post-injury and increased over the study decade (R2 = 0.806). In a multi-variable analysis, variables most strongly associated with receipt of a neurostimulant were age 14-18 years (odds ratio 5.8, 95% confidence interval [4.3,7.8]), motor vehicle collision (3.1, [2.4,4.2]), intracranial pressure (ICP) monitor (3.8, [3.1,4.5]), and mechanical ventilation (3.4, [2.7,4.3]). Use of neurostimulants following pediatric TBI is uncommon, has increased over time, and is associated with indicators of higher severity of illness. Knowledge of prescribing practices may assist in optimizing the design of efficacy and outcome studies that will inform clinical guidelines.

Medication Use as a Contributor to Fluid Overload in the PICU: A Prospective Observational Study.

In this prospective observational study, we explored the association of daily fluid intake from medication use with fluid overload in 75 children beginning 24 hours after intubation. The mean percent daily fluid intake from medications was 29% in the overall cohort. Excess intake and inadequate output contributed significantly to fluid overload. In the 28 patients who became ≥10% fluid overloaded, the mean percent daily fluid intake from medications was 34%, but just 23% in the patients who did not. Awareness of volume contribution and maximized concentration of parenteral medications when able may lessen the burden of fluid overload.

A Quality Assessment of a Collaborative Model of a Pediatric Antimicrobial Stewardship Program.

BACKGROUND: Infectious Diseases Society of America guidelines recommend that key antimicrobial stewardship program (ASP) personnel include an infectious disease (ID) physician leader and dedicated ID-trained clinical pharmacist. Limited resources prompted development of an alternative model by using ID physicians and service-based clinical pharmacists at a pediatric hospital. The aim of this study was to analyze the effectiveness and impact of this alternative ASP model. METHODS: The collaborative ASP model incorporated key strategies of education, antimicrobial restriction, day 3 audits, and practice guidelines. High-use and/or high-cost antimicrobial agents were chosen with audits targeting vancomycin, caspofungin, and meropenem. The electronic medical record was used to identify patients requiring day 3 audits and to communicate ASP recommendations. Segmented regression analyses were used to analyze quarterly antimicrobial agent prescription data for the institution and selected services over time. RESULTS: Initiation of ASP and day 3 auditing was associated with blunting of a preexisting increasing trend for caspofungin drug starts and use and a significant downward trend for vancomycin drug starts (relative change -12%) and use (-25%), with the largest reduction in critical care areas. Although meropenem use was already low due to preexisting requirements for preauthorization, a decline in drug use (-31%, P = .021) and a nonsignificant decline in drug starts (-21%, P = .067) were noted. A 3-month review of acceptance of ASP recommendations found rates of 90%, 93%, and 100% for vancomycin, caspofungin, and meropenem, respectively. CONCLUSIONS: This nontraditional ASP model significantly reduced targeted drug usage demonstrating acceptance of integration of service-based clinical pharmacists and ID consultants.

Implementation of a standardized process for ordering and dispensing of high-alert emergency medication infusions.

OBJECTIVES: Pharmacies encounter challenges when ensuring safe, timely medication dispensing to patients in the pediatric intensive care unit, when high-alert medications are needed in emergent situations. Removal of these medications from nursing stock presented challenges to providing timely administration to critical patients. The project's purpose was to develop a new method for reducing dispensing time while improving patient safety in pediatric intensive care units. METHODS: A committee of physicians, nurses, a clinical pharmacist, and pharmacy administration collaborated for process development. The process established a list of compounded, ready-to-use infusions stored in the pharmacy, immediately available for dispensing. The dispensing mechanism includes ordering and dispensing processes using an "Urgent Drip Request" form. Most frequently ordered infusions (dopamine, epinephrine, norepinephrine) were added to automated dispensing cabinets in critical care units in concentrations that could be safely infused centrally or peripherally. RESULTS: During the initial 4 months, 71 "Urgent Drip Request" sheets were processed. Drug utilization evaluation demonstrated a dispensing time of less than 1 minute for drip medications leaving the pharmacy after the form was received. No sheets processed exceeded the institutional 30-minute turnaround time, nor were errors or delays documented. Limited turnaround time data existed preimplementation but was not robust enough for analysis. It was not ethically feasible to perform a head-to-head comparison with the previous method, as it might have resulted in delay of therapy and negative patient outcomes. CONCLUSIONS: This program allows high-alert medication infusion availability in an expedited manner, removes potential for compounding errors at the bedside, and assures clean room preparation. This has improved pharmacy efficiency in provision of safe patient care to critically ill pediatric patients.

Antibiotic therapy in neonatal and pediatric septic shock.

Severe sepsis accounts for nearly 4,500 deaths (mortality rate 10%), and is responsible for nearly $2 billion annual healthcare expenditure in the United States. Early and speedy treatment of critically ill septic patients can halt or reduce the likelihood of physiologic progression to multi-system organ failure. A cornerstone of this therapeutic strategy is antibiotic administration. In this review, we discuss the empirical treatment strategies for the treatment of early and late neonatal sepsis, along with pediatric sepsis. Furthermore, we discuss the rationale that underlies the adoption of such treatment strategies. The present article also discusses the emergence of multi-drug organisms as the causative agents for sepsis, i.e. methicillin-resistant Staphylococcus aureus (MRSA), resistant enterococci and Klebsiella pneumoniae carbapenemases (KPC).

Immunoparalysis and nosocomial infection in children with multiple organ dysfunction syndrome.

PURPOSE: Immunoparalysis defined by prolonged monocyte human leukocyte antigen DR depression is associated with adverse outcomes in adult severe sepsis and can be reversed with granulocyte macrophage colony-stimulating factor (GM-CSF). We hypothesized that immunoparalysis defined by whole-blood ex vivo lipopolysaccharide-induced tumor necrosis factor-alpha (TNFα) response <200 pg/mL beyond day 3 of multiple organ dysfunction syndrome (MODS) is similarly associated with nosocomial infection in children and can be reversed with GM-CSF. METHODS: In study period 1, we performed a multicenter cohort trial of transplant and nontransplant multiple organ dysfunction syndrome (MODS) patients (≥2 organ failure). In study period 2, we performed an open-label randomized trial of GM-CSF therapy for nonneutropenic, nontransplant, severe MODS patients (≥3 organ failure) with TNFα response <160 pg/mL. RESULTS: Immunoparalysis was observed in 34% of MODS patients (n = 70) and was associated with increased nosocomial infection (relative risk [RR] 3.3, 95% confidence interval [1.8-6.0] p < 0.05) and mortality (RR 5.8 [2.1-16] p < 0.05). TNFα response <200 pg/mL throughout 7 days after positive culture was associated with persistent nosocomial infection, whereas recovery above 200 pg/mL was associated with resolution of infection (p < 0.05). In study period 2, GM-CSF therapy facilitated rapid recovery of TNFα response to >200 pg/mL by 7 days (p < 0.05) and prevented nosocomial infection (no infections in seven patients versus eight infections in seven patients) (p < 0.05). CONCLUSIONS: Similar to in adults, immunoparalysis is a potentially reversible risk factor for development of nosocomial infection in pediatric MODS. Whole-blood ex vivo TNFα response is a promising biomarker for monitoring this condition.