Carglumic acid enhances rapid ammonia detoxification in classical organic acidurias with a favourable risk-benefit profile: A retrospective observational study

BACKGROUND: Isovaleric aciduria (IVA), propionic aciduria (PA) and methylmalonic aciduria (MMA) are inherited organic acidurias (OAs) in which impaired organic acid metabolism induces hyperammonaemia arising partly from secondary deficiency of N-acetylglutamate (NAG) synthase. Rapid reduction in plasma ammonia is required to prevent neurological complications. This retrospective, multicentre, open-label, uncontrolled, phase IIIb study evaluated the efficacy and safety of carglumic acid, a synthetic structural analogue of NAG, for treating hyperammonaemia during OA decompensation. METHODS: Eligible patients had confirmed OA and hyperammonaemia (plasma NH3 > 60 μmol/L) in ≥1 decompensation episode treated with carglumic acid (dose discretionary, mean (SD) first dose 96.3 (73.8) mg/kg). The primary outcome was change in plasma ammonia from baseline to endpoint (last available ammonia measurement at ≤18 hours after the last carglumic acid administration, or on Day 15) for each episode. Secondary outcomes included clinical response and safety. RESULTS: The efficacy population (received ≥1 dose of study drug and had post-baseline measurements) comprised 41 patients (MMA: 21, PA: 16, IVA: 4) with 48 decompensation episodes (MMA: 25, PA: 19, IVA: 4). Mean baseline plasma ammonia concentration was 468.3 (±365.3) μmol/L in neonates (29 episodes) and 171.3 (±75.7) μmol/L in non-neonates (19 episodes). At endpoint the mean plasma NH3 concentration was 60.7 (±36.5) μmol/L in neonates and 55.2 (±21.8) μmol/L in non-neonates. Median time to normalise ammonaemia was 38.4 hours in neonates vs 28.3 hours in non-neonates and was similar between OA subgroups (MMA: 37.5 hours, PA: 36.0 hours, IVA: 40.5 hours). Median time to ammonia normalisation was 1.5 and 1.6 days in patients receiving and not receiving concomitant scavenger therapy, respectively. Although patients receiving carglumic acid with scavengers had a greater reduction in plasma ammonia, the endpoint ammonia levels were similar with or without scavenger therapy. Clinical symptoms improved with therapy. Twenty-five of 57 patients in the safety population (67 episodes) experienced AEs, most of which were not drug-related. Overall, carglumic acid seems to have a good safety profile for treating hyperammonaemia during OA decompensation. CONCLUSION: Carglumic acid when used with or without ammonia scavengers, is an effective treatment for restoration of normal plasma ammonia concentrations in hyperammonaemic episodes in OA patients

Consideraciones prácticas sobre la nutrición enteral en el recién nacido prematuro/Practical considerations about enteral nutrition in the premature newborn

Premature newborns have especial functional and nutritional characteristics that, depending on their birth weight and their gestational age, are the basis to carry out their nutritional support. They need an effective and precocious nutrition in order to improve their outcome. The maintenance of an adequate extra uterine growth, an optimum energy intake, and a decrease of early morbidity are the main objectives of artificial nutrition. Energy, fluid, proteins, carbohydrates and lipids requirements of this kind of patients are shown in the present article. As well as energetic substrate, the enteral nutrition also stimulates the intestinal mucosa, influencing the acquisition of an appropriate microbiota, and it helps to create an appropriate bond between mother and baby and a suitable psychomotor maturation. The different feeding procedures for these patients are reviewed as well as the progression way to complete enteral feeding, the digestive intolerance and the selection of a diet before hospital discharge. [PUBLICATION ABSTRACT

Documento de consenso SENPE/SEGHNP/ANECIPN/SECP sobre vías de acceso en nutrición enteral pediátrica

Standardization of clinical procedures has become a desirable objective in contemporary medical practice. To this effect, the Spanish Society of Parenteral and Enteral Nutrition (SENPE) has endeavoured to create clinical practice guidelines and/or documents of consensus as well as quality standards in artificial nutrition. As a result, the SENPE’s Standardization Team has put together the “Document of Consensus in Enteral Access for Paediatric Nutritional Support” supported by the Spanish Society of Pediatric Gastroenterology, Hepatology and Nutrition (SEGHNP), the National Association of Pediatric and Neonatal Intensive Care Nursery (ANECIPN), and the Spanish Society of Pediatric Surgery (SECP). The present publication is a reduced version of our work; the complete document will be published as a monographic issue. It analyzes enteral access options in the pediatric patient, reviews the levels of evidence and provides the team-members’ experience. Similarly, it details general and specific indications for pediatric enteral support, current techniques, care guidelines, methods of administration and complications of each enteral access. The data published by the American Society for Parenteral and Enteral Nutrition (ASPEN) and several European Societies has also been incorporatedLa estandarización de procedimientos clínicos se ha convertido en un objetivo deseable en la práctica médica actual. La Sociedad Española de Nutrición Parenteral y Enteral (SENPE) está haciendo un considerable esfuerzo para desarrollar guías clínicas y/o documentos de consenso así como marcadores de calidad en nutrición artificial. Como fruto de ese esfuerzo el Grupo de Estandarización de SENPE ha elaborado un Documento de Consenso sobre Vías de Acceso en Nutrición Enteral Pediátrica, avalado también por la Sociedad Española de Gastroenterología, Hepatología y Nutrición Pediátrica (SEGHNP), la Asociación Nacional de Enfermería de Cuidados Inten- sivos Pediátricos y Neonatales (ANECIPN) y la Sociedad Española de Cirugía Pediátrica (SECP). Esta publicación es una síntesis del documento consensuado que ha incluido el estudio en profundidad del acceso enteral pediátrico, la revisión de los niveles de evidencia y la experiencia de los componentes del Grupo. Se han considerado también los datos publicados por la American Society for Parenteral and Enteral Nutrition (ASPEN) y por diversas sociedades europeas. El texto completo se publicará como un número monográfico. En este trabajo se detallan las indicaciones generales y específicas de la nutrición enteral pediátrica, las técnicas, los cuidados generales y específicos, el modo de administración y las complicaciones de las diversas vías de acces