早产儿黄疸防治进展 复旦大学附属儿科医院 新生儿科 王瑾 2015 年 8 月海口. 新生儿高胆红素血症 — 传统标准  生化意义 — 高胆红素血症 血清总胆红素大于等于 2mg/dL ( 34umol/L ) 血清总胆红素大于等于 2mg/dL ( 34umol/L )  足月儿 12mg/dL.

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Presentation transcript:

早产儿黄疸防治进展 复旦大学附属儿科医院 新生儿科 王瑾 2015 年 8 月海口

新生儿高胆红素血症 — 传统标准  生化意义 — 高胆红素血症 血清总胆红素大于等于 2mg/dL ( 34umol/L ) 血清总胆红素大于等于 2mg/dL ( 34umol/L )  足月儿 12mg/dL ( 205 至 222umol/L )  早产儿 15mg/dL

新生儿高胆红素血症 (Neonatal hyperbilirubinemia)  动态变化过程  诊断高胆红素血症时需考虑日龄  采用 Bhutani 新生儿时龄胆红素列线图 95 百分位以上为高危区 —— 需干预的高胆红素血症 百分位为中高危区 百分位为中低危区 40 百分位以下为低危区

时龄胆红素曲线 Pediatrics 103 : 6-14 , 1999

胆红素脑病相关神经毒性因素 小孕周低出生体重低体温窒息能量衰竭 低蛋白血症 延长的高胆红素血症 败血症 酸中毒 过度溶血

早产儿胆红素脑病  缺乏典型症状:呼吸暂停 循环呼吸功能急剧恶化 循环呼吸功能急剧恶化  不易诊断  低出生体重儿甚至在 10-14mg/dL 即可发生 胆红素脑病

Pediatrics International , 2015 , 57 : VLBW 胆红素脑病诊断

新生儿黄疸处理  黄疸监测,判断高胆危险区  进一步完善病史,家族史,体格检查  实验室检查  制定诊疗方案

早产儿黄疸  近足月早产儿, ≥35 周 AAP 指南  < 35 周?, VLBW ?, ELBW ?

胆红素监测方法  目测胆红素、经皮胆红素  血清胆红素(总胆 / 直接 / 间接)  血浆游离胆红素(未于白蛋白结合)  胆红素产生速率 血清碳氧血红蛋白( COHb )水平 血清碳氧血红蛋白( COHb )水平 呼出气一氧化碳( ETCOc )水平 呼出气一氧化碳( ETCOc )水平

目测胆红素 — 足月儿 胆红素换算 1 mg/dl = 17.1  mol/L Discuss and Repeat Call MD now No concerns

经皮胆红素 — 足月儿  足月儿广泛应用  安全性、可靠性  与 TsB 相关性(特定范围)  用于监测随访

经皮胆红素 — 早产儿 TcB 是应用于 VLBW 高胆有效、 无创的筛查工具

血清胆红素 VLBW 峰值血清胆红素

VLBW 的 PSB 和预后 生后 2 周内 PSB 和 ELBW 死亡、 NID 、听力损害、 PDI < 70 相关

胆红素结合力与游离胆红素  总胆红素本身局限性,无法可靠预测新生儿发生 BIND 或核黄疸  仅依赖总胆红素水平可导致光疗过度 / 延迟应用

孕周与 BBC 新生儿胆红素结合能力

BBC 应用于光疗或换血的阈值 胆红素结合能力 : Lamola,Bhutani and Du. Peds Res 2015 推荐共识 : Maisels. J Perinatol % 45% 45% BBC: 光疗 67% BBC: 换血

发生胆红素所致神经功能障碍理论风险 Lamola,Bhutani and Du. Pediatric Research 2015 麻烦 危险 有害 观察 麻烦 危险 麻烦

BBC 测定:血液荧光法

呼气末二氧化碳 (ETCO) 溶血诊断 血型 血型 Coombs’ 试验阳性 Coombs’ 试验阳性 高胆红素血症 高胆红素血症 Hb 水平下降 Hb 水平下降 网织红细胞, 球形红细胞增加 网织红细胞, 球形红细胞增加 碳氧血红蛋白增加 * / ETCO 碳氧血红蛋白增加 * / ETCO

血清碳氧血红蛋白( COHb ) 无溶血 ( N=14 ) 溶血 ( N=10 ) P 值 ETCO ( ppm ) 1.8±1.12.9± * COHb ( % ) 1.6±0.52.3± Hb(g/L) h 182.8± ± Ret(%)3.1±1.64.9± STB(umol/L)323.4± ±

时龄胆红素曲线临床应用 Pediatrics 103 : 6-14 , 1999

时龄胆红素列线图临床应用 高危区:光疗后 4-8 小时内评估 TSB 中高危区:光疗后 4-24 小时内评估 TSB/TcB 中低危区: <72 小时出院, 2 天内随访 TSB 低危区: <72 小时出院, 2 天内随访 Avery , 9th

新生儿高胆红素血症治疗 监测随访胆红素高危因素高胆找病因(病因治疗)提早开奶,胎粪排出

早产儿干预标准 TSB ( mg/dL ) <24h<48h<72h<96h<120h≥120h BW光疗换血光疗换血光疗换血光疗换血光疗换血光疗换血 <1000g g g g g 新生儿高胆红素血症诊断和治疗专家共识 中华儿科杂志 2014 , 52 ( 10 )

Pediatrics 2004;114: Guidelines for phototherapy in hospitalized infants of 35 or more weeks' gestation

Arch dis child , 2003

早产儿光疗 — 积极 vs. 保守

积极光疗 / 保守光疗定义  积极光疗 BW501 ~ 750g : ≥5mg/dL 开始 / 继续 / 重新开始 BW751 ~ 1000g : 日龄 7 天内 ≥5mg/dL ; 日龄 7 ~ 14 天 ≥7mg/dL 日龄 7 ~ 14 天 ≥7mg/dL  保守光疗 BW501 ~ 750g : ≥8mg/dL BW501 ~ 750g : ≥8mg/dL BW751 ~ 1000g : ≥10mg/dL BW751 ~ 1000g : ≥10mg/dL

结果

治疗方法  水化  光疗  换血  抑制溶血:静脉丙球;增加结合:白蛋白应用  抑制重吸收(肠肝循环)  抑制胆红素产生:锡原卟啉

光疗

ELBW 不同光疗设备比较

影响光疗效力因素及作用  灯光光谱,波长 nm 最强  病人和光源间距离  暴露于光疗下的表面积  光疗光线输出能量:普通约 10W/cm 2 /nm 强光 > 30W/cm 2 /nm 强光 > 30W/cm 2 /nm

光疗强度测定仪

光疗副作用  发热,脱水(经皮肤水分丢失)  皮疹(红斑)  腹泻  氧化损伤,降低核黄素  紫外线( UV )光辐射  青铜症

停止光疗  TSB<222 ~ 239µmol/L ( 13 ~ 14mg/dL )  TSB 低于光疗阈值胆红素 50µmol/L ( 3mg/dL )以下  强光疗时 TSB 低于换血阈值胆红素 50µmol/L ( 3mg/dL ) 以下时改标准光疗 标准光疗: 8 ~ 10 µW/ ( cm 2.nm ) 强光疗: 30 µW/ ( cm 2.nm )

新生儿换血 当积极光疗不能控制迅速升高的胆红素水平,胆红素脑病 危险明显超过换血本身的危险时才应用

美国各年< 1500g 早产儿换血人数 Arch dis child , 2003

换血途径 入出特点 脐静脉 脐动脉 传统途径、需中心置管无菌操作 脐静脉 外周动脉 宜堵管、速度较慢、需中心置 外周静脉 脐动脉 需中心置管无菌操作 外周静脉 脐静脉 需中心置管无菌操作 外周静脉 外周动脉 宜堵管、速度较慢

Guidelines for exchange transfusion in infants 35 or more weeks' gestation Pediatrics 2004;114:

换血指征  AAP 推荐换血标准:时龄胆红素值  严重溶血,出生脐血 TsB>76mmol/L ( 4.5mg/dL ), Hb 76mmol/L ( 4.5mg/dL ), Hb<110g/L ,伴水肿、肝脾大、心衰  有急性胆红素脑病表现  附加: B/A 值

换血中检测实验室指标  胆红素  电解质、血糖  血常规  凝血功能  动脉血气分析

白蛋白的应用  血浆白蛋白水平:胆红素接近换血且白蛋白< 25g/L  特别是低蛋白早产儿  胆红素 / 白蛋白比值( B/A ) <0.5 胆红素易与白蛋白联结 >1 游离胆红素   易与神经细胞联结

风险分类 应考虑换血的 B/A 比值 TSBmg/dL/Alb , g/dL TSBμmol/L/Alb , μmol/L 患儿 ≥ 38 0/7 周 患儿 35 0/7-36 6/7 周并 健康或 ≥ 38 0/7 周,如 果有更高风险或同族 免疫性溶血性疾病或 G6PD 缺乏症 患儿 35 0/7-36 6/7 周, 如果有更高风险或或 同族免疫性溶血性疾 病或 G6PD 缺乏症

其它药物应用  静脉丙球: 1g / kg ,封闭 Fc 受体 → 抑制溶血 必要时 12 小时重复 必要时 12 小时重复  锡原卟啉:抑制血红素加氧酶,减少胆红素生成  肝酶诱导剂:鲁米那,肝酶活性 ↑→ 增加结合

卟啉在 VLBW 中应用  SnMP 单剂 4.5mg/Kg ,肌注,出生 46 小时用药

谢 谢! 谢 谢!