精氨酸加压素受体拮抗剂治疗抗利尿激素不适当分泌综合征的疗效和安全性初步观察

目的 观察精氨酸加压素受体拮抗剂托伐普坦对抗利尿激素不适当分泌综合征（SIADH）患者低钠血症的治疗效果和安全性.方法 选择确诊为SIADH患者6例,4例分配至托伐普坦组,口服托伐普坦15～60 mg每日一次,根据监测的血钠水平调整给药剂量;2例分配至常规治疗组,给予常规治疗,限制入量1 000 ml/d,根据监测的血钠结果,予低于3％氯化钠静脉输注并配合分次口服盐胶囊10～15 g/d,观察处理第4,7天的血钠水平与基线血钠水平的变化量、血钠水平首次达到正常的时间、治疗期间患者24 h尿量、体质量变化.所有患者治疗前后进行安全性评估,包括病史、体检、心电图、实验室检查、不良事件发生率等.结果 托伐普坦组中各例患者血钠水平在治疗第1天开始上升,病例1,2,3,4治疗第4天的血钠水平较基线分别升高了22,16,14,11 mmol/L;常规治疗组患者的血钠水平较基线无明显变化.托伐普坦组中病例1,2,3,4治疗第7天血钠水平较基线分别升高了14,13,14,13 mmol/L;常规治疗组中仅病例2的血钠水平较基线升高了4 mmol/L,且常规治疗组患者在治疗期间血钠水平均未达到正常低限.托伐普坦组的所有患者在治疗1d后尿量开始增加,第3天后趋于稳定,治疗期间24h尿量均大于1 500ml.常规治疗组患者在观察期间24 h尿量780 ～1 400 ml,与治疗前比较无明显变化.两组患者治疗后体质量与治疗前比较有所下降,托伐普坦组患者体质量降低幅度略明显.两组患者治疗前后的血压、心率无明显变化,均在正常范围.观察过程中未发现严重并发症及不良事件.结论 精氨酸加压素受体拮抗剂托伐普坦较常规治疗方法更能有效纠正SIADH患者低钠血症、减轻水潴留且安全性好.

Preliminary observation of efficacy and safety of arginine vasopressin receptor antagonist in the treatment of syndrome of inappropriate secretion of antidiuretic hormone

Objective To observe the efficacy and safety of arginine vasopressin receptor antagonist tolvaptan for treating hyponatremia caused by syndrome of inappropriate secretion of antidiuretic hormone （SIADH）.Methods Six patients diagnosed with SIADH were enrolled in this study.Four cases were allocated to tolvaptan group （oral tolvaptan 15-60 mg/d,the dosage was adjusted based on the level of serum sodium）.Two cases were allocated to regular treatment group （liquid was limited 1 000 ml/d,intravenous drip was less than 3％ sodium chloride and/or oral salt capsule 10-15 g/d several times was adjusted based on the level of serum sodium）.Data of the level of serum sodium at 4,7 d,baseline value of serum sodium,serum sodium at the first normal time,24 h urine and weight change were collected.Safety assessment was given before and after treatment,including medical history,physical examination,electrocardiogram,laboratory tests,and incidence of adverse events.Results The level of serum sodium in tolvaptan group increased from the first day of the treatment.During the period of treatment,serum sodium at 4 d increased 22,16,14,11 mmol/L compared with the baseline value respectively.No obvious change of sodium was observed in regular treatment group compared with the baseline value.For 7 d treatment,serum sodium level increased 14,13,14,13 mmol/L in tolvaptan group compared with the baseline level respectively.Only 2 cases in regular treatment group increased 4 mmol/L,and sodium level in regular treatment group did not reach the lower limit of normal level of serum sodium.In tolvaptan group,all patients urine output increased after 1 d treatment and began to stabilize in 3 d.24 h urine putouts were much more than 1 500 ml during treatment.Urine putouts 780-1 400 ml were observed in regular treatment group.There was no difference before and after treatment.Although weight dropped after treatment in the two groups,weight in tolvaptan group fell obviously.In the two groups,there was no difference in blood pressure and heart rate before and after treatment.There were no serious complications and adverse events.Conclusions Compare with regular treatment,arginine vasopressin receptor antagonist is more effective therapy because it can correct the SIADH in patients with hyponatremia and reduce water retention.It also has a good security.