Stability of N-Acetylcysteine (NAC) in Standardized Pediatric Parenteral Nutrition and Evaluation of N,N-Diacetylcystine (DAC) Formation.

The ESPGHAN/ESPEN/ESPR-Guidelines on pediatric parenteral nutrition (PPN) recommend the administration of the semiessential amino acid (AA) cysteine to preterm neonates due to their biochemical immaturity resulting in an inability to sufficiently synthetize endogenous cysteine. The soluble precursor N-acetylcysteine (NAC) is easily converted into bioavailable cysteine. Its dimer N,N-diacetylcystine (DAC) is almost unconvertable to cysteine when given intravenously resulting in a diminished bioavailability of cysteine. This study aims to understand the triggers and oxidation process of NAC to DAC to evaluate possibilities of reducing DAC formation in standardized PPN. Therefore, different air volumes (21% O2) were injected into the AA compartment of a standardized dual-chamber PPN. O2 concentrations were measured in the AA solution and the headspaces of the primary and secondary packaging. NAC and DAC concentrations were analyzed simultaneously. The analysis showed that O2 is principally delivered from the primary headspace. NAC oxidation exclusively delivers DAC, depending on the O2 amount in the solution and the headspaces. The reaction of NAC to DAC being containable by limiting the O2 concentration, the primary headspace must be minimized during manufacturing, and oxygen absorbers must be added into the secondary packaging for a long-term storage of semipermeable containers.

Drug-related problems identification in general internal medicine: The impact and role of the clinical pharmacist and pharmacologist.

BACKGROUND: Patients admitted to general internal medicine wards might receive a large number of drugs and be at risk for drug-related problems (DRPs) associated with increased morbidity and mortality. This study aimed to detect suboptimal drug use in internal medicine by a pharmacotherapy evaluation, to suggest treatment optimizations and to assess the acceptance and satisfaction of the prescribers. METHODS: This was a 6-month prospective study conducted in two internal medicine wards. Physician rounds were attended by a pharmacist and a pharmacologist. An assessment grid was used to detect the DRPs in electronic prescriptions 24h in advance. One of the following interventions was selected, depending on the relevance and complexity of the DRPs: no intervention, verbal advice of treatment optimization, or written consultation. The acceptance rate and satisfaction of prescribers were measured. RESULTS: In total, 145 patients were included, and 383 DRPs were identified (mean: 2.6 DRPs per patient). The most frequent DRPs were drug interactions (21%), untreated indications (18%), overdosages (16%) and drugs used without a valid indication (10%). The drugs or drug classes most frequently involved were tramadol, antidepressants, acenocoumarol, calcium-vitamin D, statins, aspirin, proton pump inhibitors and paracetamol. The following interventions were selected: no intervention (51%), verbal advice of treatment optimization (42%), and written consultation (7%). The acceptance rate of prescribers was 84% and their satisfaction was high. CONCLUSION: Pharmacotherapy expertise during medical rounds was useful and well accepted by prescribers. Because of the modest allocation of pharmacists and pharmacologists in Swiss hospitals, complementary strategies would be required.

Evaluation of tools to prevent drug incompatibilities in paediatric and neonatal intensive care units.

OBJECTIVE: Intravenous drug administration in neonatal (NICU) and paediatric intensive care units (PICU) is critical because of poor venous access, polymedication, fluid restriction and low infusion rate. Risk is further increased by inadequate information on the physicochemical compatibility of drugs. Eight decision-supporting tools were hence evaluated to improve the detection of drug incompatibilities in paediatric wards. SETTING: NICU and PICU, University hospital. METHOD: Eight tools (Thériaque 2007, Stabilis 3, Perfysi 2 databases; KIK 3.0 software; Neofax 2007 handbook; King 2008 Guide, CHUV 9.0, pH 2007 cross-tables) were assessed by two pharmacists using 40 drug pairs (20 incompatible; 20 compatible) frequently prescribed in PICUs and NICUs. Trissel's 14th Ed. handbook served as the gold standard. Four criteria were evaluated (each with a maximum of 250 points): accuracy (sensitivity, specificity, positive and negative predictive values), completeness (number of drug pairs documented), comprehensiveness (presence of 16 different items), and applicability (by combining the time needed by 7 pharmacists to classify 5 drug pairs, plus an evaluation of their design, usefulness, reliability and ergonomics, using visual analogy scales). The percentage of non-compliant answers (NCA) was calculated for both the performing pharmacists and the tools. MAIN OUTCOME MEASURE: Global score of drug incompatibilities (accuracy + completeness + comprehensiveness + applicability). RESULTS: Thériaque obtained the best global score (840/1000 points), followed by pH (807), CHUV (803), Perfysi (776), Neofax (678), King Guide (642), Stabilis (584) and KIK (523), respectively. The highest scores were reached by Thériaque for accuracy (234/250); Thériaque and pH for completeness (200/250); Thériaque and Perfysi for comprehensiveness (218/250); and pH for applicability (298/250). The range of pharmacists' NCAs was between 9% (4/45 NCAs) and 33% (15/45), whereas that for drug pairs was between 10% (6/63) and 30% (19/63). The range of NCAs for tools was between 6% (2/35, pH) and 49% (18/35, Perfysi). CONCLUSIONS: Thériaque proved outstanding as a drug-incompatibility tool. However, all resources showed some shortcomings. The large ranges of pharmacists' NCAs shows that such an assessment is subject to different interpretations. Standard operating procedures for drug-incompatibility assessment should be implemented in drug-information centres. Tools with low NCA percentage, such as the pH or CHUV tables, may be useful for nurses in ICUs.

Long-term physico-chemical stability of standard parenteral nutritions for neonates.

BACKGROUND & AIMS: Two ready-to-use parenteral nutritions (PN) have been developed, for the first days of life of the premature newborn, along with syringes of lipid emulsion with or without vitamins. Long-term physico-chemical stability for storage in wards was assessed. METHODS: Physico-chemical stability of PN: visual inspection, particle size, pH, osmolarity measurement, amino acids, glucose, and electrolytes dosages. Physico-chemical stability of lipid emulsion: visual inspection, globule size, peroxide level and vitamins A, E, and C dosages. Stability was studied for 12 weeks on refrigerated (2-8 °C) and room temperature (30 ± 2 °C) samples. RESULTS: No precipitation was detected in any PN. A brown coloration was observed in PN stored for four weeks at room temperature but not in the refrigerator. Concentrations of all the nutrients remained constant over the 12 week-study period. Phase separation of the lipid emulsion occurred after three weeks, but particle size complied with the USP limits for 12 weeks. Peroxide content increased only in the samples without vitamins at room temperature. Vitamins remained stable for one week under refrigeration. CONCLUSION: The PN did not present a detectable change of the tested properties when refrigerated for 12 weeks. The lipid emulsion with vitamins is stable for one week when refrigerated.