脂肪乳治疗地西泮中毒的临床研究

Treatment of diazepam intoxication with lipid emulsion:clinical study

目的观察脂肪乳对地西泮中毒患者疗效及血药浓度的影响。方法 26例重度地西泮中毒患者按中毒严重程度大致接近原则,分为氟吗西尼组(单纯氟吗西尼治疗,9例);10%脂肪乳组(氟吗西尼+10%脂肪乳250 mL治疗,9例);20%脂肪乳组(氟吗西尼+20%脂肪乳250 mL治疗,8例)。比较各组间治疗前、后不同时间点(治疗后1、10和20 h)血液地西泮浓度以及病人住院时间、氟吗西尼总用量差异。结果治疗前各组地西泮血药浓度差异无统计学意义(P>0.05),治疗后不同时间点各组间地西泮血药浓度比较差异均有统计学意义(P=0.000),两个脂肪乳组血药浓度均明显低于单纯氟吗西尼组。其中治疗后1 h,20%脂肪组明显低于10%脂肪乳组[(1 952.3±837.4)ng/mL、(2 428.9±1149.3)ng/mL,P=0.033];治疗后10 h和20 h 10%脂肪乳组与20%脂肪乳组浓度差异无统计学意义[(1 786.9±899.4)ng/mL、(1 359.1±665.6)ng/mL,P>0.05;(1 362.1±792.1)ng/mL、(1 090.5±638.4)ng/mL,P>0.05]。氟吗西尼总用量组间比较,差异有统计学意义(P=0.000)。氟吗西尼组(3.33±0.80)mg与10%脂肪乳组(2.26±0.36)mg及20%脂肪乳组(1.91±0.29)mg相比,差异均有统计学意义(P=0.000)。住院时间组间比较,差异有统计学意义(F=20.594,P=0.000)。氟吗西尼组(5.23±1.23)d与10%脂肪乳组(3.60±0.80)d及20%脂肪乳组(2.50±0.58)d差异均有统计学意义(P=0.000);10%脂肪乳组与20%脂肪乳组差异有统计学意义(P=0.017)。结论脂肪乳可在短时间内降低地西泮血药浓度,减少中毒患者氟吗西尼用量,缩短住院时间,是地西泮或其他脂溶性药物中毒的潜在解毒剂。

Objective To investigate therapeutic efficacy of lipid emulsion in diazepam intoxication and its influence on blood toxicant concentration. Methods Based on approximate same severity,26 severe diazepam intoxication patients were divided into flumazenil group（n=9,flumazenil alone）,10% lipid emulsion group（n=9,flumazenil ＋ 250 mL 10% lipid emulsion,abbreviated as 10% group） and 20% lipid emulsion group（n=8,flumazenil ＋ 250 mL 20% lipid emulsion,abbreviated as 20% group）.The differences of blood diazepam concentration at different time points（before treatment,1 h,10 h and 20 h after treatment）,duration of hospital stay and overall dosages of flumazenil in three groups were compared respectively.Results The differences in blood diazepam concentration had no statistical significance before treatment between the 3 groups（P0.05）,while after treatment,the differences at different time points had statistical significance（P=0.000）.The blood toxicant concentration was significantly lower in lipid emulsion groups than in the flumazenil group.One hour after treatment,the blood diazepam concentration was significantly lower in 20% group than in 10% group（1 952.3± 837.4 ng/mL VS 2 428.9±1 149.3 ng/mL,P=0.033）.Ten hours and 20 hours after treatment,the differences in blood toxicant concentration between 10% and 20% groups were statistically insignificant（1 786.9±899.4 ng/mL VS 1 359.1±665.6 ng/mL,P0.05;1 362.1±792.1 ng/mL VS 1 090.5±638.4 ng/mL,P0.05）.The overall dosages of flumazenil showed statistical significance of difference between the 3 groups（P=0.000） and between flumazenil group（3.33±0.80） mg and both 10% group（2.26±0.36） mg and 20% group（1.91±0.29） mg（P=0.000）.The differences in duration of hospital stay showed statistical significance between the 3 groups（F=20.594,P=0.000）,between the flumazenil group（5.23±1.23） days and both 10% group（3.60±0.80） days and 20% group（2.50±0.58） days（P=0.000） and between 10% group and 20% group（P=0.017）.Conclusion Lipid emulsion could lower blood toxicant concentration in diazepam intoxication patients in a short period,reduce the dosage of flumazenil used and shorten the duration of hospital stay,thus may be a potential antidote for intoxication of diazepam or other lipid solubility drugs.