钙剂补充改善献血者柠檬酸盐抗凝剂相关副反应的研究

Effect of oral and intravenous calcium supplementation on the improvement of acute citrate-related symptoms

目的了解不同钙剂补充方式对改善献血者柠檬酸盐抗凝剂相关副反应的效果。方法在获得知情同意后,对22名年龄匹配的志愿者应用自身交叉、安慰剂对照研究模式,在一定的间隔期内分别实施了3次标准化条件下的临床干预方案,A:持续80min,按1.5mg.kg-1.min-1输注柠檬酸盐抗凝剂;B:A+输注前10min口服1.2g钙剂;C:A+静脉输注葡萄糖酸钙100mg/h。在干预实施的同时记录受试者对柠檬酸盐抗凝剂输注的反应,并采集不同观测时间点血样做游离钙离子浓度(iCa2+)检测。结果柠檬酸盐相关副反应主要表现为口唇、面部、肢体麻木、胸闷、头晕、恶心等轻、中度反应;临床干预40、80和干预结束后120min时,A组与C组相比,iCa2+(mmol/L)分别为1.00±0.05vs1.06±0.05、0.94±0.06vs1.04±0.06、1.22±0.05vs1.30±0.05(P<0.01),两组副反应发生率对比为54.55%vs18.18%(P<0.05),而A组vsB组这2项指标的差异无统计学意义(P>0.05);A组中的男性与女性相比,干预终末点iCa2+(mmol/L)为0.98±0.04vs0.90±0.06(P<0.01),副反应发生率为13.64%vs40.91%(P<0.05)。副反应的发生与干预性补钙终末点的iCa2+密切相关(r=-0.52,P=0.01)而与试验对象的体重无关(r=-0.238,P=0.286)。结论本研究模式下,静脉补钙比口服补钙能够更加有效地改善柠檬酸盐所致低钙血症并减少相关副反应的发生;以口服补钙作为预防措施时则需在服用剂量和服用时间上多加考虑。对女性献血者在机采血液前进行常规性的预防性补钙是有益的。

Objective To evaluate the effect of oral and intravenous calcium supplementation on improvement of the adverse citrate reactions.Methods A crossover,placebo-controlled study was conducted.Twenty two volunteers were enrolled after informed consents were obtained.Volunteers received 3 standardized interventions containing：A,citrate infusion for 80 minutes at the dose of 1.5 mg·kg^-1·min^-1;B,infusion of A plus 1.2 g oral calcium administration 10 minutes before citrate infusion;C,infusion of A plus simultaneous intravenous infusion of calcium at the rate of 100mg/h.During the observation period,Citrate toxicity symptoms were recorded and serial blood samples were collected for the determination of ionized calcium level.Results The most frequent symptoms due to citrate administration were anaesthesia of labia oris,prosopo and limbs,chest distress,dizziness and nausea etc.Compared to A,treatment C significantly increased serum level of ionized calcium （C vs A,P0.01） and reduced the frequency of citrate-related symptoms （C vs A,P0.05）,no such effects were observed in treatment B.Moreover,female had lower serum level of ionized calcium （t=3.47,P0.01） at the end of citrate infusion and had higher frequency of citrate-related symptoms （P=0.03） than male.The occurrence of adverse reactions was correlated to the serum level of ionized calcium at the end of citrate infusion （r=-0.52,P=0.01）,but not to the individual body weight （r=-0.238,P=0.286）.Conclusion Intravenous infusion of calcium is more effective than oral calcium for the improvement of citrate-induced hypocalcemia and for the reduction of citrate toxicity.Administration of oral calcium as a preventive measure during apheresis should take into account the dose and the timing of administration.We recommend routine calcium supplementation for female apheresis platelet donors.