改良水化方法对哩来麟酸注射液急性期反应的影响

Effects of modified hydration method on acute-phase reaction of zoledronic acid injection

目的探讨自行建立的改良水化方法对唑来膦酸注射液(密固达)急性期反应(APR)的影响。方法研究设计为随机对照试验。研究对象选自2016年8月至2017年12月因风湿病合并骨质疏松症收入首都医科大学宣武医院风湿免疫科、拟接受首次或二次密固达治疗的患者。将符合纳入标准的患者随机分为改良水化组和常规水化组。改良水化组患者在静脉滴注密固达前、后滴注0.9%氯化钠注射液各500 ml,用药前、后2 h内在护士照护下应用量水模具饮水各750 ml,总入液量>2500 ml;常规水化组患者仅被叮嘱在静脉滴注密固达前、后多饮水,要求总饮水量>2000 ml,但未提供量水模具,用药后用0.9%氯化钠注射液100 ml冲管,总入液量>2000 ml。比较2组患者用药后3 d内APP发生情况和用药后第3天Scr水平的差异。结果共190例患者纳入研究,改良水化组100例,常规水化组90例,2组患者性别分布、年龄、首次与二次应用密固达者比例、用药前最低骨密度T值及用药前Scr水平比较,差异均无统计学意义(均P>0.05)。静脉滴注密固达后3 d内改良水化组APR发生率和发热发生率均明显低于常规水化组[40.0%(40/100)比68.9%(62/90),P<0.01;23.0%(23/100)比44.4%(40/90),P<0.01]。改良水化组中首次和二次用药者APR发生率和发热发生率均明显低于常规水化组中相同用药次数者[首次用药:53.3%(32/60)比73.6%(39/53),30%(18/60)比50.9%(27/53);二次用药:20%(8/40)比62.2%(23/37),12.5%(5/40)比35.1%(13/37)],二次用药者APR发生率和乏力发生率均明显低于首次用药者[20.0%(8/40)比53.3%(32/60),17.5%(7/40)比41.7%(25/60)];常规水化组中二次用药者头痛发生率明显低于首次用药者[0%(0/37)比13.2%(7/53)];上述差异均有统计学意义(均P<0.05)。改良水化组和常规水化组均无一例患者出现急性肾损伤,Scr水平分别为(52±20)和(52±13)μmol/L。结论改良水化方法可有效降低首次与二次使用密固达患者的APR发生率。

ObjectiveTo explore the effects of self-established method of modified hydration on the acute-phase reaction(APR)of zoledronic acid injection.MethodsThis study was designed as randomized controlled trial.The subjects were inpatients with rheumatism and osteoporosis who were intended to receive zoledronic acid injection for the first or second time in Department of Rheumatology&Immunology,Xuanwu Hospital,Capital Medical University from August 2016 to December 2017.The patients who meet the inclusion criteria were randomly divided into the modified hydration group and the routine hydration group.The patients in the modified hydration group received IV infusions of 0.9%sodium chloride injection 500 ml before and after IV infusion of zoledronic acid injection,respectively and water 750 ml measured with mould under the care of nurses within 2 hours before and after medication,respectively.The total amount of liquid was more than 2500 ml.The patients in the routine hydration group were only told to drink a large amount of water before and after IV infusion of zoledronic acid injection.The total amount of liquid was required to be more than 2000 ml,but the water measuring mould was not provided.After IV infusion,the intravenous infusion tube was washed by 0.9%sodium chloride injection 100 ml.The total amount of liquid was more than 2000 ml.The incidence of APR within 3 days of medication and levels of serum creatine on day 3 of medication in patients in the 2 groups were compared.ResultsA total of 190 patients were enrolled in the study,including100 and 90 patients in the modified hydration group and the routine hydration group,respectively.The differences of sex distribution,age,proportion of patients with zoledronic acid injection for the first or second time,minimum bone mineral density T value before medication,and the levels of serum creatine before medication between the 2 groups were not statistically significant(P>0.05 for all).The incidences of APR and fever in the modified hydration group were significantly lower than those in the routine hydration group[40.0%(40/100)vs.68.9%(62/90),P<0.01;23.0%(23/100)vs.44.4%(40/90),P<0.01]within 3 days of IV infusion of zoledronic acid injection.The incidences of APR and fever in patients treatment with zoledronic acid injection for the first or second time in the modified hydration group were significantly lower than those in the routine hydration group[first medication:53.3%(32/60)vs.73.6%(39/53),30%(18/60)vs.50.9%(27/53);second medication:20.0%(8/40)vs.62.2%(23/37),12.5%(5/40)vs.35.1%(13/37)];the incidences of APR and weakness in patients treatment with zoledronic acid injection for the second time were significantly lower than those for the first time[20.0%(8/40)vs.53.3%(32/60),17.5%(7/40)vs.41.7%(25/60)];the incidence of headache in patients treatment with zoledronic acid injection for the second time in the routine hydration group were significantly lower than those for the first time[0(0/37)vs.13.2%(7/53)];all above-mentioned differences were statistically significant(P<0.05 or P<0.01).No patients developed acute kidney injury in the 2 groups.The levels of serum creatine in the 2 groups were(52±20)and(52±13)μmol/L,respectively.ConclusionThe modified hydration method can decrease the incidence of APR effectively in patients with zoledronic acid injection treatment for the first or second time.