Development and Stability of a New Formulation of Pentobarbital Suppositories for Paediatric Procedural Sedation

Pentobarbital is a drug of choice to limit motion in children during paediatric procedural sedations (PPSs). However, despite the rectal route being preferred for infants and children, no pentobarbital suppositories are marketed, and therefore they must be prepared by compounding pharmacies. In this study, two suppository formulations of 30, 40, 50, and 60 mg of pentobarbital sodium were developed using hard-fat Witepsol® W25 either alone (formulation F1) or with oleic acid (formulation F2). The two formulations were subjected to the following tests described in the European Pharmacopoeia: uniformity of dosage units, softening time, resistance to rupture, and disintegration time. The stability of both formulations was also investigated for 41 weeks of storage at 5 ± 3 °C using a stability-indicating liquid chromatography method to quantify pentobarbital sodium and research breakdown product (BP). Although both formulae were compliant to uniformity of dosage, the results were in favour of a faster disintegration of F2 compared to F1 (−63%). On the other hand, F1 was found to be stable after 41 weeks of storage unlike F2 for which several new peaks were detected during the chromatographic analysis, suggesting a shorter stability of only 28 weeks. Both formulae still need to be clinically investigated to confirm their safety and efficiency for PPS

État des lieux des systèmes supports de prise en charge médicamenteuse en psychopharmacologie des patients atteints d’une pathologie de santé mentale

L’utilisation optimale des psychotropes représente un enjeu par leur complexité d’utilisation et le poids que représentent les pathologies de santé mentale dans la population. L’objectif de ce travail a été de faire l’état des lieux des systèmes supports de prise en charge médicamenteuse en psychopharmacologie, en tenant compte des orientations actuelles de la santé mentale en France, et d’établir des propositions à développer sur notre territoire.Une revue de la littérature, de l’épidémiologie descriptive et analytique ainsi qu’une étude qualitative ont été réalisées. Un constat sur la prise en charge médicamenteuse en psychopharmacologie et l’évolution des parcours des patients atteints d’un handicap psychique a été fait. Une étude des facteurs associés à l’hospitalisation en psychiatrie a montré au travers d’une étude cas-témoin (n = 617) l’importance de prendre en compte les déterminants du patient. La littérature a révélé que les systèmes supports de prise en charge médicamenteuse en psychopharmacologie sont limités majoritairement à des outils de pharmacie clinique insuffisamment développés et à des structures d’expertise de type CRPV ou centres experts d’accès difficile dans la pratique de soins courante. Des entretiens semi-directifs effectués auprès de 28 professionnels de santé ont permis de modéliser les obstacles et facteurs facilitant l’utilisation d’outils multidisciplinaires à la résolution de situations complexes en psychopharmacologie, et de pouvoir proposer des réponses.Deux systèmes supports pour répondre aux limites identifiées sont présentés afin d’accompagner le relais thérapeutique hôpital-ville au travers du développement de multiples actions

Table_1_Identification of factors associated with hospitalization in an outpatient population with mental health conditions: a case–control study.docx

IntroductionAddressing relevant determinants for preserved person-centered rehabilitation in mental health is still a major challenge. Little research focuses on factors associated with psychiatric hospitalization in exclusive outpatient settings. Some variables have been identified, but evidence across studies is inconsistent. This study aimed to identify and confirm factors associated with hospitalization in a specific outpatient population.MethodsA retrospective monocentric case-control study with 617 adult outpatients (216 cases and 401 controls) from a French community-based care facility was conducted. Participants had an index outpatient consultation between June 2021 and February 2023. All cases, who were patients with a psychiatric hospitalization from the day after the index outpatient consultation and up to 1 year later, have been included. Controls have been randomly selected from the same facility and did not experience a psychiatric hospitalization in the 12 months following the index outpatient consultation. Data collection was performed from electronic medical records. Sociodemographic, psychiatric diagnosis, historical issues, lifestyle, and follow-up-related variables were collected retrospectively. Uni- and bivariate analyses were performed, followed by a multivariable logistic regression.ResultsVisit to a psychiatric emergency within a year (adjusted odds ratio (aOR): 13.02, 95% confidence interval (CI): 7.32–23.97), drug treatment discontinuation within a year (aOR: 6.43, 95% CI: 3.52–12.03), history of mental healthcare without consent (aOR: 5.48, 95% CI: 3.10–10.06), medical follow-up discontinuation within a year (aOR: 3.17, 95% CI: 1.70–5.95), history of attempted suicide (aOR: 2.50, 95% CI: 1.48–4.30) and unskilled job (aOR: 0.26, 95% CI: 0.10–0.65) are the independent variables found associated with hospitalization for followed up outpatients.ConclusionsPublic health policies and tools at the local and national levels should be adapted to target the identified individual determinants in order to prevent outpatients from being hospitalized.</p

Development and Stability of a New Formulation of Pentobarbital Suppositories for Paediatric Procedural Sedation

Pentobarbital is a drug of choice to limit motion in children during paediatric procedural sedations (PPSs). However, despite the rectal route being preferred for infants and children, no pentobarbital suppositories are marketed, and therefore they must be prepared by compounding pharmacies. In this study, two suppository formulations of 30, 40, 50, and 60 mg of pentobarbital sodium were developed using hard-fat Witepsol® W25 either alone (formulation F1) or with oleic acid (formulation F2). The two formulations were subjected to the following tests described in the European Pharmacopoeia: uniformity of dosage units, softening time, resistance to rupture, and disintegration time. The stability of both formulations was also investigated for 41 weeks of storage at 5 ± 3 °C using a stability-indicating liquid chromatography method to quantify pentobarbital sodium and research breakdown product (BP). Although both formulae were compliant to uniformity of dosage, the results were in favour of a faster disintegration of F2 compared to F1 (−63%). On the other hand, F1 was found to be stable after 41 weeks of storage unlike F2 for which several new peaks were detected during the chromatographic analysis, suggesting a shorter stability of only 28 weeks. Both formulae still need to be clinically investigated to confirm their safety and efficiency for PPS