2例咪达唑仑致新生儿肌阵挛矛盾反应并文献复习

Two cases of neonatal myoclonus paradoxical response induced by midazolam and literature review

目的总结2例咪达唑仑致新生儿肌阵挛矛盾反应的临床特点并结合相关文献进行复习,以提高临床对苯二氮[艹卓]类致矛盾反应的认识。方法描述我院2例咪达唑仑致新生儿肌阵挛的临床资料,并以“咪达唑仑/矛盾反应”、“咪达唑仑/肌阵挛”为检索词,检索建库至2019年11月的中文数据库(中国知网数据库、万方数据库);以“midazolam/paradoxical response”、“midazolam/myoclonus”为检索词,检索2010年1月至2019年11月的PubMed数据库,进行文献复习。结果共检索出英语文献11篇,中文文献2篇,共119例患者。咪达唑仑致矛盾反应临床特点:儿童及成人予以标准剂量咪达唑仑均可出现矛盾反应,男性发生率明显高于女性,发病间隔时间为0~15 min,均数为(4.63±4.56)min。所有患者表现为肢体异常运动,形式多种多样,年长儿及成人主要表现为明显异常的哭吵、坐立不安、激动、焦虑、沮丧、狂躁、具有攻击性、肢体颤动等,6例新生儿则全部表现为肌阵挛或抽搐。除去文献中未描述治疗方案的51例患者,停用咪达唑仑患者7例,使用氟马西尼拮抗62例,氟马西尼联合丙泊酚治疗1例,治愈率100%。结论虽然矛盾反应发生率低,且没有生命危险,但考虑到苯二氮[艹卓]类药物应用广泛,因此,仍需考虑此类药物使用中存在的相关问题,早期识别和快速药物干预对于避免病情加重非常重要。具有矛盾反应危险因素,如男性、年龄小于3岁的患者,可积极联用非苯二氮[艹卓]类药物,减少苯二氮[艹卓]类使用剂量,且降低药物的推注速度,可能有助于防止发生矛盾反应。氟马西尼是苯二氮[艹卓]类药物的拮抗剂,可用于治疗苯二氮卓类致矛盾反应。

Objective To summarize the clinical characteristics of two cases of neonatal myoclonic paradoxical response caused by midazolam and review the relevant literature to improve the clinical understanding of benzodiazepine-induced paradoxical reactions.Methods The clinical data of 2 cases of neonatal myoclonus caused by midazolam in our hospital were described,and“midazolam/paradoxical response”and“Midazolam/Myoclonus”were used as the search term to search the databases until November 2019 in Chinese databases(Chinese National Knowledge Infrastructure database,Wanfang Database);also,“midazolam/paradoxical response”and“Midazolam/Myoclonus”were used as the search term to search from PubMed database January 2010 to November 2019;and literature review was performed.Results A total of 119 patients in 11 English literatures and 2 Chinese literatures were retrieved.Clinical characteristics of paradoxical response caused by midazolam were as follows:paradoxical response could occur in children and adults with standard dose of midazolam;the incidence was significantly higher in male than in female;the interval between onsets was 0~15 min,and the average was(4.63±4.56)min.All patients showed abnormal movements of limbs in various forms.Older children and adults mainly showed obvious abnormal crying,restlessness,agitation,anxiety,depression,mania,aggressiveness and limb tremor,etc.,and all 6 neonates manifested myoclonus or convulsions.Excluding 51 patients whose treatment regimen was not described in the literature,7 patients discontinued midazolam,62 patients were treated with flumazenil,and 1 patient was treated with flumazenil combined with propofol,the cure rate being 100%.Conclusion Although the incidence of paradoxical response is low and it is not life-threatening,considering the widespread use of benzodiazepines,it is still necessary to consider the related problems in the use of such drugs.Early identification and rapid drug intervention are very important to avoid exacerbations.If risk factors with paradoxical response are present,such as male,or patients younger than 3 years of age,it is advised to actively use non-benzodiazepines,reduce the dose of benzodiazepines,and slow down the bolus speed of the drug to help prevent paradoxical response.Flumazenil is an antagonist of benzodiazepines and can be used to treat benzodiazepine-induced paradoxical response.