Anesthetic management of pediatric patients with Niemann‐Pick disease type C for intrathecal 2‐hydroxypropyl‐β‐cyclodextrin injection

Abstract

Background Niemann‐Pick disease type C is an autosomal‐recessive, lysosomal storage disorder with variable age of onset and a heterogeneous clinical presentation that includes neurological, psychiatric, and visceral findings. Serial intrathecal injections of 2‐hydroxypropyl‐beta‐cyclodextrin are being evaluated as a treatment modality for Niemann‐Pick disease type C with a subset of patients requiring anesthesia for this procedure. Aims The aim of this study was to evaluate the safety of anesthesia provided for patients undergoing intrathecal injection of 2‐hydroxypropyl‐beta‐cyclodextrin. Methods A retrospective review of pediatric patients who received serial intrathecal injections of 2‐hydroxypropyl‐beta‐cyclodextrin with anesthesia at two tertiary care centers was conducted from December 2015 through April 2019. Data were extracted for analysis included preoperative comorbidities, demographics, vital signs, intraoperative anesthesia course, airway management technique, venous access, postoperative course, and perioperative complications. In total, 19 patients were identified and a total of 394 anesthetic encounters were included in this study. Results All 394 2‐hydroxypropyl‐beta‐cyclodextrin administration procedures were successfully performed, and there were no changes made in the anesthetic plan during the anesthesia encounters. Three hundred forty‐nine anesthetics were performed utilizing inhalation induction and mask maintenance, and 45 anesthetics were performed with placement of a supraglottic airway device due to patient body habitus and provider preference. The incidence of a major adverse event (aspirations, arterial desaturation) was 5/394 (1.3%, 95% CI 0.05%‐3.1%). Minor adverse events (emesis, delirium, hypotension, seizure, and airway obstruction) were observed in 19/394 encounters (4.8%, 95% CI 3.0%‐7.5%). Conclusions Our findings suggest that general anesthesia induced via inhalation induction and maintained with volatile anesthetic via mask or supraglottic airway is a safe and effective option for pediatric patients with Niemann‐Pick disease type C undergoing serial intrathecal injections of 2‐hydroxypropyl‐beta‐cyclodextrin, supporting this technique as a viable option for anesthetic care in these patients.

Human iPSC-Based Models for the Development of Therapeutics Targeting Neurodegenerative Lysosomal Storage Diseases

“…This is the case of the lipid chelators 2-hydroxypropyl-β-cyclodextrin (HPBCD) and 2-hydroxypropyl-γ-cyclodextrin (HPGCD), which favor the degradation/exocytosis of macromolecules through the generation of inclusion complexes with cholesterol, sphingomyelin, lipids and GM2 gangliosides in in vitro models of NPC ( Soga et al, 2015 ), Niemann–Pick disease type A (NPA) ( Long et al, 2016 ), Neuronal Ceroid Lipofucinosis (NCL) ( Sima et al, 2018 ) and Tay-Sachs disease (TSD) ( Vu et al, 2018 ). Studies on hiPSC-derived NPC neural cultures showed a dose-dependent neurotoxic effects of HPBCD ( Long et al, 2016 ), which is currently used to treat NPC patients ( Matsuo et al, 2013 ; Ory et al, 2017 ; Hastings et al, 2019 ; Ulloa et al, 2020 ), thus anticipating recent in vivo studies showing a region-specific alteration of the homeostasis of different lipid species in the brain of HPBCD-treated mice with potential detrimental effects that should to be carefully evaluated ( Long et al, 2016 ; Glaser et al, 2020 ).…”