Li Yan,Zhang Congzhi,Yin Shunhua,et al.Preliminary study of analgesic during infusion of GD2 monoclonal antibody naxitamab in children[J].Journal of Clinical Pediatric Surgery,2023,22(07):630-634.[doi:10.3760/cma.j.cn101785-202303043-006]
儿童输注GD2单克隆抗体Naxitamab期间的镇痛方案初探
- Title:
- Preliminary study of analgesic during infusion of GD2 monoclonal antibody naxitamab in children
- Keywords:
- Antibodies; Monoclonal; Analgesia; Molecular Targeted Therapy; Surgical Procedures; Operative; Child
- 摘要:
- 目的 初步探讨儿童输注GD2单克隆抗体Naxitamab期间的镇痛方案。方法 本研究为回顾性研究，选择海南省妇女儿童医学中心博鳌分院2021年8月至2023年2月期间32例难治性神经母细胞瘤患儿进行的167次Naxitamab输注疗程为研究对象，总结输注Naxitamab引起的疼痛发生特点、部位、持续时间及不良反应。为了缓解输注期间出现的疼痛，采用以口服加巴喷丁作为基础镇痛、复合静脉应用强效镇痛药来控制爆发性疼痛的方案。根据所应用强效镇痛药种类的不同，分为芬太尼组、艾斯氯胺酮组、氢吗啡酮联合艾斯氯胺酮组共3组，整个输注过程将患儿的疼痛控制在FLACC评分≤4分。结果 芬太尼组、艾斯氯胺酮组、氢吗啡酮联合艾斯氯胺酮组三组患儿在每次输注期间发生疼痛（FLACC评分>4分）的次数分别是（3.17±1.23）次、（2.98±2.18）次、（3.07±2.02）次，差异无统计学意义（F=0.413，P>0.05）；三组输注完成所用时长分别是（63.4±32.6）min、（59.7±45.6）min、（64.6±48.9）min，差异无统计学意义（F=0.811，P>0.05）；氢吗啡酮联合艾斯氯胺酮组所需艾斯氯胺酮剂量为（1.22±2.68）mg/kg，显著低于艾斯氯胺酮组所需艾斯氯胺酮剂量（2.64±2.36）mg/kg（P<0.05）；三组主要不良反应：低血氧饱和度发生例次分别为28、33、26次，差异无统计学意义（χ2=0.462，P>0.05）；低平均动脉压发生例次分别为36、39、23次，差异无统计学意义（χ2=0.689，P>0.05）。结论 以口服加巴喷丁为基础镇痛，静脉应用起效迅速的芬太尼或艾斯氯胺酮来抑制Naxitamab输注引起的爆发性疼痛安全、有效；选择镇痛时效较长的氢吗啡酮联合艾斯氯胺酮同样能达到抑制疼痛的效果。
- Abstract:
- Objective To explore the analgesic regimen of children during an infusion of GD2 monoclonal antibody naxitamab.Methods For this retrospective study, 167 naxitamab infusions were administered in 32 children with refractory neuroblastoma from August 2021 to February 2023 at Bo’ao Branch of Hainan Women & Children’s Medical Center.summarized the characteristics, location, duration and adverse reactions of pain caused by infusion.For relieving pain during infusion, a protocol with oral gabapentin as base analgesic was formulated with an intravenous infusion of potent compound analgesics.According to the uses of different analgesics, they were divided into three groups of fentanyl, esketamine and hydromorphone plus esketamine.The overall target was pain relief as judged by FLACC (Face, Legs, Activity, Cry, Consolability) ≤ 4 points.Results The number of occurrence of pain (FLACC score ≥ 4) during a single infusion in three groups was (3.17±1.23), (2.98±2.18) and (3.07±2.02) respectively.No statistically significant differences existed among three groups (F=0.413, P>0.05).The average time of a single infusion in three groups was (63.4±32.6), (59.7±45.6) and (64.6±48.9) min.No statistically significant differences existed among three groups (F=0.811, P>0.05).However, in the hydromorphone combined esketamine group, the dose of esketamine of mg/kg was significantly less than the dose in A group[(1.22±2.68) vs.(2.64±2.36), P<0.05].No significant difference existed in the incidence of major adverse reactions among three groups, such as low oxygen saturation[(28/51), (33/62) & (26/45), χ2=0.462, P>0.05].The number of cases of low mean arterial pressure was[(36/51), (39/62) & (23/45) (χ2=0.689, P>0.05)].Conclusion Oral gabapentin as a basic analgesic plus an intravenous infusion of fentanyl or esketamine are both safe and effective for pain bouts due to an infusion of naxitamab.And a combination of hydromorphone and esketamine can also achieve excellent analgesia.
参考文献/References:
[1] Ahmed M, Cheung NKV.Engineering anti-GD2 monoclonal antibodies for cancer immunotherapy[J].FEBS Lett, 2014, 588(2):288-297.DOI:10.1016/j.febslet.2013.11.030.
[2] Navid F, Sondel PM, Barfield R, et al.Phase I trial of a novel anti-GD2 monoclonal antibody, Hu14.18K322A, designed to decrease toxicity in children with refractory or recurrent neuroblastoma[J].J Clin Oncol, 2014, 32(14):1445-1452.DOI:10.1200/JCO.2013.50.4423.
[3] Cheung IY, Kushner BH, Modak S, et al.Phase I trial of anti-GD2 monoclonal antibody hu3F8 plus GM-CSF:impact of body weight, immunogenicity and anti-GD2 response on pharmacokinetics and survival[J].Oncoimmunology, 2017, 6(11):e1358331.DOI:10.1080/2162402X.2017.1358331.
[4] Yu AL, Gilman AL, Ozkaynak MF, et al.Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma[J].N Engl J Med, 2010, 363(14):1324-1334.DOI:10.1056/NEJMoa0911123.
[5] Irwin MS, Naranjo A, Zhang FF, et al.Revised neuroblastoma risk classification system:a report from the children’s oncology group[J].J Clin Oncol, 2021, 39(29):3229-3241.DOI:10.1200/JCO.21.00278.
[6] Ladenstein R, P?tschger U, Valteau-Couanet D, et al.Investigation of the role of dinutuximab beta-based immunotherapy in the SIOPEN high-risk neuroblastoma 1 trial (HR-NBL1)[J].Cancers (Basel), 2020, 12(2):309.DOI:10.3390/cancers12020309.
[7] Nickel FT, Seifert F, Lanz S, et al.Mechanisms of neuropathic pain[J].Eur Neuropsychopharmacol, 2012, 22(2):81-91.DOI:10.1016/j.euroneuro.2011.05.005.
[8] Juhl H, Petrella EC, Cheung NK, et al.Additive cytotoxicity of different monoclonal antibody-cobra venom factor conjugates for human neuroblastoma cells[J].Immunobiology, 1997, 197(5):444-459.DOI:10.1016/s0171-2985(97)80078-2.
相似文献/References:
[1]陈立才,李朋飞,黄一敏,等. 抗EpCAM单克隆抗体治疗肝母细胞瘤的动物实验研究[J].临床小儿外科杂志,2019,18(01):63.
Chen Licai,Li Pengfei,Huang Yimin,et al. Targeting therapy of antiEpCAM monoclonal antibody in hepatoblastoma animal model.[J].Journal of Clinical Pediatric Surgery,2019,18(07):63.
备注/Memo
收稿日期:2023-03-15。
基金项目:海南省临床医学中心建设项目资助（琼卫医函, 2021]75号）
通讯作者:李艳,Email:xh52ly@126.com