Nimodipine systemic exposure and outcomes following aneurysmal subarachnoid hemorrhage: a pilot prospective observational study (ASH-1 study)
Notice bibliographique
Résumé
Background Nimodipine improves outcomes following aneurysmal subarachnoid hemorrhage (aSAH). Guidelines recommend that all patients should receive a fixed-dose nimodipine for 21 days. However, studies reported variability of nimodipine concentrations in aSAH. It is not clear if reduced systemic exposure contributes to worsening outcomes. The aim of this study was to compare nimodipine systemic exposure in those who experienced poor outcomes to those who experienced favorable outcomes. Methods This was a pilot prospective observational study in 30 adult patients admitted to the University of Alberta Hospital with aSAH. Data were collected from the electronic health records following enrollment. Blood samples were collected around one nimodipine 60 mg dose at a steady state, and nimodipine [total, (+)-R and (−)-S enantiomers] plasma concentrations were determined. The poor outcome was defined as a modified Rankin Scale (mRS) score at 90 days of 3-6, while the favorable outcome was an mRS score of 0-2. The correlation between nimodipine concentrations and percent changes in mean arterial pressure (MAP) before and after nimodipine administration was also determined. Furthermore, covariates potentially associated with nimodipine exposure were explored. Results In total, 20 (69%) participants had favorable outcomes and 9 (31%) had poor outcomes. Following the exclusion of those with delayed presentation (>96 h from aSAH onset), among those presented with the World Federation of Neurological Surgeons (WFNS) grade 3–5, nimodipine median (interquartile range) area under the concentration time curve (AUC0-3h) in those with favorable outcomes were 4-fold higher than in those with poor outcomes [136 (52–192) vs. 33 (23–39) ng.h/mL, respectively, value of p = 0.2]. On the other hand, among those presented with WFNS grade 1–2, nimodipine AUC0-3h in those with favorable outcomes were significantly lower than in those with poor outcomes [30 (28–36) vs. 172 (117–308) ng.h/mL, respectively, value of p = 0.03)]. (+)-R-nimodipine AUC0-3h in those who did not develop vasospasm were 4-fold significantly higher than those who had vasospasm (value of p = 0.047). (−)-S-nimodipine was significantly correlated with percentage MAP reduction. Similar results were obtained when the whole cohort was analyzed. Conclusion The study was the first to investigate the potential association between nimodipine exposure following oral dosing and outcomes. In addition, it suggests differential effects of nimodipine enantiomers, shedding light on the potential utility of nimodipine enantiomers. Larger studies are needed.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».