Lo Emily, Cizmeci Mehmet N, Wilson Diane, Ly Linh G, El-Shahed Amr, Offringa Martin, Pierro Agostino, Kalish Brian T
Division of Neonatology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, M5G 1X8, Canada.
Child Health Evaluative Sciences, SickKids Research Institute, 686 Bay Street, Toronto, ON, M5G 1L7, Canada.
Pediatr Res. 2024 Oct 12. doi: 10.1038/s41390-024-03625-2.
Despite implementation of therapeutic hypothermia (TH) for infants with neonatal encephalopathy (NE), a significant proportion of infants suffer neurodevelopmental impairment (NDI). Remote ischemic conditioning (RIC) is a proposed neuroprotective maneuver that has been studied in adults with brain injury, but it has not been previously investigated in infants with NE.
We performed a prospective, randomized, safety and dose escalation study in 32 neonates with NE. Four cohorts of consecutive patients were randomized to RIC therapy, including four cycles of limb ischemia and reperfusion on progressive days of TH, or sham. Clinical, biochemical, and safety outcomes were monitored in both groups.
All patients received the designated RIC therapy without interruption or delay. RIC was not associated with increased pain, vascular, cutaneous, muscular, or neural safety events. There was no difference in the incidence of seizures, brain injury, or mortality between the two groups with the escalation of RIC dose and frequency.
We found that RIC is a safe and feasible adjunctive therapy for neonates with NE undergoing TH.
This pilot study establishes critical safety and feasibility data that are necessary for the design of future studies to investigate the potential efficacy of RIC to reduce NDI.
Remote ischemic conditioning (RIC) is a possible neuroprotective intervention in infants with hypoxic-ischemic encephalopathy (HIE). RIC can be administered concurrently with therapeutic hypothermia without any notable adverse events. Future studies will need to address potential efficacy of RIC to improve neurodevelopmental outcomes, as well as consider the ideal temporal window and dose for RIC in this patient population.
尽管对患有新生儿脑病（NE）的婴儿实施了治疗性低温（TH），但仍有相当一部分婴儿遭受神经发育障碍（NDI）。远程缺血预处理（RIC）是一种提议的神经保护措施，已在脑损伤成人中进行了研究，但此前尚未在患有NE的婴儿中进行研究。
我们对32例患有NE的新生儿进行了一项前瞻性、随机、安全性和剂量递增研究。连续的四组患者被随机分配接受RIC治疗，包括在TH进行的连续几天进行四个周期的肢体缺血和再灌注，或假手术。两组均监测临床、生化和安全性结果。
所有患者均不间断或延迟地接受了指定的RIC治疗。RIC与疼痛、血管、皮肤、肌肉或神经安全性事件增加无关。随着RIC剂量和频率的增加，两组之间癫痫发作、脑损伤或死亡率的发生率没有差异。
我们发现RIC对于接受TH的患有NE的新生儿是一种安全可行的辅助治疗。
这项初步研究建立了关键的安全性和可行性数据，这些数据对于设计未来研究以调查RIC减少NDI的潜在疗效是必要的。
远程缺血预处理（RIC）对于患有缺氧缺血性脑病（HIE）的婴儿可能是一种神经保护干预措施。RIC可与治疗性低温同时进行，且无任何明显不良事件。未来的研究需要探讨RIC改善神经发育结局的潜在疗效，并考虑该患者群体中RIC的理想时间窗和剂量。
