唑类抗真菌药物加剧儿童急性淋巴细胞白血病长春碱相关低钠血症

Antifungal Azoles Exacerbate Vinblastine-related Hyponatremia in ALL Children

本研究旨在探讨唑类抗真菌药物加剧儿童急性淋巴细胞白血病(ALL)患儿化疗时长春碱相关低钠血症的临床特点及治疗方法。2013年4月-2014年3月在我科给予长春碱化疗的93例患儿纳入本研究,分为3组:VDLD组,VDLD加唑类抗真菌药物组,VDLD加非唑类抗真菌药物组;统计分析各组低钠血症的发生率及低钠血症的严重程度。结果表明:1低钠血症发生率在VDLD组为93.1%(67/72),VDLD加唑类抗真菌药物组为100%(13/13),VDLD加非唑类抗真菌药物组为75%(6/8),各组间无统计学差异;2中-重度低钠血症(血清Na<129mmol/L)发生率在VDLD加唑类抗真菌药物组为69.2%(9/13),明显高于VDLD组(30.6%,22/72)(P=0.008)和VDLD加非唑类抗真菌药物组(12.5%,1/8)(P=0.011);而在VDLD组与VDLD加非唑类抗真菌药物组间无差异(P=0.284);3最低血钠水平在VDLD加唑类抗真菌药物组为124.0±8.6 mmol/L,显著低于VDLD组(130.8±3.8mmol/L)(P<0.001)及VDLD加非唑类抗真菌药物组(132.9±4.9 mmol/L)(P<0.001),而在VDLD组与VDLD加非唑类抗真菌药物组间无差异(P=0.246);4 4例严重低血钠患儿发生抽搐、昏迷,血清钠浓度111-123 mmol/L,均为VDLD加唑类抗真菌药物组患儿。低钠血症的患儿,经限制液体入量,调整液体张力,补充高渗钠及利尿,血清钠值逐步回升,随访4-11个月无再出现低钠血症。结论:长春碱治疗ALL低钠血症发生率高,多无症状。唑类抗真菌药与长春碱联合应用,可增加低钠血症的严重程度,故在长春碱用药期间应避免采用唑类抗真菌药防治真菌感染。

The purpose of this study was to investigate the clinical characteristics and the treatments of patients with vinblastine-related hyponatremia which was aggravated by azole antifungal agents in children with acute lymphoblastic leukemia（ALL）.A total of 93 children treated with vinblastine in our department during April 2013 to March 2014 were enrolled in this study and were divided into 3 groups：VDLD,VDLD with azoles antifungal,VDLD with non azoles antifungal.The incidence and severity of hyponatremia were statistically analysed.The results showed that （1） the incidence of hyponatremia in VDLD group was 93.1% （67/72）,100% （13/13） in VDLD with azoles antifungal group,and 75% （6/8） in VDLD with non-azoles antifungal,there was no statistically difference between these three groups.（2） Incidence of moderate to severe hyponatremia （Na 〈 129 mmol/L） in VDLD with azoles antifungal group was（9/ 13,69.2%）,which was significartly higher than those in VDLD group（22/72,30.6%） and in VDLD with non azoles antifungal group （1/8,12.5%）.However,the difference between VDLD group and VDLD with non azoles antifungal group were not statistical significant.（3） the lowest serum sodium level in VDLD with azoles antifungal group （124.0 ±8.6 mmol/L） was significantly lower than that in VDLD group（130.8 ± 3.8 mmol/L） and VDLD ＋ non azoles antifungal group（132.9 ± 4.9mmol/L）.Otherwise,the difference was not statistically significant between VDLD group and VDLD with non azoles antifungal group.（4） four children with severe hyponatremia showed convulsions and coma which all belong to VDLD with azoles antifungal group.The children with hyponatremia were restricted intake of fluid,adjusted the liquid tension,supplied hypertonic sodium and given diuretic,the serum sodium value gradually picked up in these children.In 4-11 months＇ follow-up,no hyponatremia happened again in these children.It is concluded that the incident of hyponatremia in children treated with vinblastine is high,but most of them seldom showed clinical characteristics.The combination of antifungal azoles with vinblastine can increase the incidence and severity of hyponatremia.Therefore,combined administration of azole antifungals with vinblastine should be avoided.