Offering Guidance and Learning to Prescribers to Initiate Parenteral Nutrition using a Validated Electronic Decision TREE (OLIVE TREE).

Parenteral nutrition (PN) is recommended in patients nutritionally at risk and unable to receive oral or enteral nutrition. A standardized electronic PN order format could enhance appropriate PN prescribing. We developed the OLIVE TREE (Offering guidance and Learning to prescribers to Initiate PN using a Validated Electronic decision TREE), embedded in our electronic health record. We aimed to evaluate its validity and impact on physicians' prescribing behavior. A non-randomized before-after study was carried out in a tertiary care center. The OLIVE TREE comprises 120 individual items. A process validation was performed to determine interrater agreement between a pharmacist and the treating physician. To estimate the proportion of patients for whom the OLIVE TREE had an effective and potential impact on physicians' prescribing behavior, a proof of concept study was conducted. The proportion of patients for whom PN was averted and the proportion of decisions not in line with the recommendation were also calculated. The process validation in 20 patients resulted in an interrater agreement of 95.0%. The proof of concept in 73 patients resulted in an effective and potential impact on prescribing behavior in 50.7% and 79.5% of these patients, respectively. Initiation of PN was not averted and recommendations of the OLIVE TREE were overruled in 42.5% of the patients. Our newly developed OLIVE TREE has a good process validity. A substantial impact on prescribing behavior was observed, although initiation of PN was not avoided. In the next phase, the decision tree will be implemented hospital-wide.

Supplementation of vitamins, trace elements and electrolytes in the PEPaNIC Randomised Controlled Trial: Composition and preparation of the prescription.

BACKGROUND AND AIMS: Following the results of the paediatric early versus late parenteral nutrition in critical illness (PEPaNIC) multicentre, randomised, controlled trial, the new ESPGHAN/ESPEN/ESPR/CSPEN and ESPNIC guidelines recommend to consider withholding parenteral macronutrients for 1 week, while providing micronutrients, in critically ill children if enteral nutrition is insufficient. Critically ill children are suspected to be vulnerable to micronutrient deficiencies due to inadequate enteral nutrition, increased body's demands and excessive losses. Hitherto, micronutrient requirements in PICU are estimated based on recommended daily intakes for healthy children and expert opinion. We aimed to provide an overview of the current practice of micronutrient administration and practical considerations in the three participating centres of the PEPaNIC study, and compare these therapies with the recommendations in the new ESPGHAN/ESPEN/ESPR/CSPEN guidelines. METHODS: We describe the current composition and preparation of the prescribed parenteral micronutrients (consisting of vitamins, trace elements and electrolytes) in the three centres (Leuven, Rotterdam and Edmonton) that participated in the PEPaNIC RCT, and compare this per micronutrient with the ESPGHAN/ESPEN/ESPR/CSPEN guidelines recommendations. RESULTS: The three centres use a different micronutrient supplementation protocol during the first week of critical illness in children, with substantial differences regarding the amounts administered. Leuven administers commercial vitamins, trace elements and electrolytes in separate infusions both in 4 h. Rotterdam provides commercial vitamins and trace elements simultaneously via 8-h infusion and electrolytes continuously over 24 h. Lastly, Edmonton administers commercial vitamins and institutionally prepared trace elements solutions in 1 h and electrolytes on demand. Comparison with the ESPGHAN/ESPEN/ESPR/CSPEN guidelines yields in differences between the recommendations and the administered amounts, which are most substantial for vitamins. CONCLUSION: The practice of intravenous micronutrient administration differs substantially between the three PEPaNIC centres and in comparison with the current guideline recommendations. This deviation is at least partially explained by the inability to provide all recommended amounts with the currently available commercial products and by the lack of strong evidence supporting these recommendations.

Beyond pancreatic insufficiency and liver disease in cystic fibrosis.

UNLABELLED: Cystic fibrosis is a life shortening hereditary disease, primarily leading to progressive pulmonary infection and exocrine pancreatic dysfunction. Several gastrointestinal complications other than malabsorption can arise during the disease course and with the progressively increasing life span of patients with CF; new and more rare complications are being recognized. We review the literature on gastrointestinal manifestations in CF, excluding the liver and pancreas. CONCLUSION: We describe the clinical presentation and treatment of more common conditions like gastroesophageal reflux, small intestinal bacterial overgrowth, intussusception, meconium ileus, distal intestinal obstruction syndrome, and constipation, and we also discuss what is known on celiac disease, appendicitis, fibrosing colonopathy, inflammation and inflammatory bowel disease and gastrointestinal cancer. WHAT IS KNOWN: • Gastrointestinal complications arise early in the course of the disease and have a severe impact on the quality of life of the patients. What is New: • This review is a concise summary of the current literature on gastrointestinal complications of cystic fibrosis. • We focused on clinical presentation and diagnostic investigations and provide a comprehensive resume of the current treatment options.

Neonatal Formulations: The Need for a Tailored, Knowledge Driven Approach.

To attain effective and safe pharmacotherapy in neonates, caregivers have to consider both the clinical characteristics of the newborn and the pharmacokinetic estimates of a given compound during prescription and administration. Overall, clearance in neonates is low when compared to other pediatric subpopulations. Despite this overall low clearance, there is already extensive between individual variability in clearance in early life. As a consequence, neonates are in urgent need of tailored drug product development that considers the need for both low and flexible dosing to maintain dose accuracy. During the development of such formulations tailored for neonates, there is also a need for guidance on excipient exposure. The available knowledge on the safety or toxicity of excipients is limited and difficult to retrieve, but there are initiatives (e.g. Safety and Toxicity of Excipients for Pediatrics [STEP] database initiative) to improve the present situation. In addition, population focussed studies on aspects of clinical pharmacology of excipients in neonates should be conducted. The propylene glycol research project and the European Study for Neonatal Excipient Exposure (ESNEE) initiative illustrate its feasibility. Finally, until tailored formulations make it to the market, compounding practices for drug formulations in neonates should be evaluated to guarantee correct dosing, product stability, safety and to support pharmacists in their daily practice.

Prospective assessment of short-term propylene glycol tolerance in neonates.

INTRODUCTION: Propylene glycol (PG) is an unintentional frequently administered solvent in neonates despite the fact that PG accumulation potentially results in hyperosmolarity, lactic acidosis and renal/hepatic toxicity. METHODS: Prospective evaluation of renal (diuresis, creatinaemia, sodium), metabolic (base excess, anion gap, lactate, bicarbonate) and hepatic (alanine transaminase, aspartate aminotransferase, direct bilirubinaemia) tolerance to PG in (pre)term neonates following intravenous administration of formulations (paracetamol, phenobarbital, digoxin) that contain PG. Observations from 48 h before up to 48 after the last PG administration were described and compared (paired analysis). Clinical characteristics and observations collected following intravenous PG-paracetamol administration were compared with a historical cohort of neonates in whom similar (renal, hepatic) observations during exposure to a mannitol-containing paracetamol formulation were collected. RESULTS: 5566 observations were collected in 69 neonates before, during and following median PG exposure of 34 mg/kg/24 h (range 14-252). Progressive postnatal adaptation in renal, metabolic and hepatic function was documented, unrelated to the PG exposure. In the subgroup of 40 cases treated with intravenous PG-paracetamol, observations on renal and hepatic function were similar to a historical cohort of published observations following exposure to intravenous mannitol-paracetamol. CONCLUSIONS: Unintended PG administration (34 mg/kg/24 h) for a maximum of 48 h seems to be tolerated in (pre)term neonates and does not affect short-term postnatal adaptations. Further studies on PG disposition and the level of safe exposure to PG, including long-term safety data in neonates are needed.

Cardiorespiratory depression and hyperglycemia after unintentional ingestion of brimonidine in a neonate.

PURPOSE: Brimonidine is a third-generation selective alpha-2 adrenergic agonist that lowers intraocular pressure by decreasing aqueous humor production and increasing uveoscleral flow. Its safety profile for children <2 years of age remains unknown. METHODS: We describe a case of ingestion of a single drop of brimonidine 0.2% in a newborn, resulting in sedation, cardiorespiratory depression, and hyperglycemia within minutes. CONCLUSIONS: This report adds to the existing evidence that brimonidine can have serious adverse side effects and should therefore be used with extreme caution in infants <2 years of age. Additionally,safety procedures like double-checking should also include vitamins or oral supplements to improve medication safety in the neonatal intensive care unit.