Supplementary Material for: Intranasal Analgosedation for Infants in the Neonatal Intensive Care Unit: A Systematic Review

<b><i>Aim:</i></b> Pain management is important for newborns’ immediate and long-term well-being. While intranasal analgesia and sedation have been well studied in children, their use could be extended to term and preterm infants. This systematic review aims to assess the use of intranasal medications for procedural analgesia or sedation in the neonatal intensive care unit. <b><i>Methods:</i></b> MEDLINE via Ovid, Scopus, Embase, and Cochrane Library were searched independently by two reviewers for clinical studies on sedation or analgesia given intranasally. <b><i>Results:</i></b> Seven studies, with 401 patients, were included. The studies described various molecules (midazolam, fentanyl, ketamine, or dexmedetomidine) for different procedures such as intubation in the delivery room, screening for retinopathy, or magnetic resonance imaging. All studies reported significant reduction in pain and sedation markers (based on clinical scales, skin conductance, and clinical variables such as heart rate and crying time). Adverse effects were uncommon and mostly consisted in desaturation, apnoea, hypotension, or paradoxical reactions. <b><i>Discussion and Conclusion:</i></b> The intranasal route seems a potential alternative for procedural pain management and sedation in neonates, especially when intravenous access is not available. However, data about safety remain limited. Reported sides effects could be attributed to molecules used rather than the intranasal route. Optimal drugs and doses still need to be characterized. Further studies are needed to ensure safety before promoting a widespread use of intranasal medications in neonatology.

<b><i>研究目的：</i></b>疼痛管理对于新生儿的即刻及远期健康均至关重要。尽管鼻内镇痛与镇静在儿童群体中的应用已得到充分研究，但其使用范围可进一步拓展至足月儿与早产儿。本系统综述旨在评估新生儿重症监护室（neonatal intensive care unit, NICU）内，经鼻给药用于操作相关镇痛或镇静的临床应用情况。<b><i>研究方法：</i></b>由两名评价员独立检索Ovid平台MEDLINE、Scopus、Embase及Cochrane图书馆数据库，查找有关经鼻给予镇静或镇痛药物的临床研究。<b><i>研究结果：</i></b>最终纳入7项临床研究，共涉及401名受试者。纳入研究涵盖了咪达唑仑、芬太尼、氯胺酮及右美托咪定等多种药物分子，用于产房气管插管、视网膜病变筛查、磁共振成像（magnetic resonance imaging, MRI）等不同临床操作。所有研究均显示，基于临床量表、皮肤电导及心率、哭闹时长等临床变量评估的疼痛与镇静指标均得到显著改善。不良反应较为少见，主要包括血氧饱和度下降、呼吸暂停、低血压或反常反应。<b><i>讨论与结论：</i></b>经鼻给药途径似乎可作为新生儿操作相关疼痛管理与镇静的潜在替代方案，尤其适用于无法建立静脉通路的场景。但目前关于其安全性的相关数据仍较为有限，已报道的不良反应或与所使用的药物分子有关，而非经鼻给药途径本身。最佳药物种类与给药剂量仍有待明确。在推广经鼻给药药物在新生儿科的广泛应用前，仍需开展进一步研究以验证其安全性。