Acute hyponatremia after aneurysmal subarachnoid hemorrhage: Frequency,treatment, and outcome

We retrospectively examined the course of serum sodium levels in 180 patients with acute aneurysmal subarachnoid hemorrhage (SAH) who had been admitted to the anesthesiologic-neurosurgical intensive care unit of the University Medical Center Regensburg, Germany, between January 2014 and December 2018. Each patient file was analyzed regarding the frequency and intensity of hyponatremic episodes and the administered medication. At admission to the intensive care unit (ICU), 18 patients had shown initial hyponatremia (<135 mmol/L) and 4 patients hypernatremia (greater than145 mmol/L). 88 (48.9%) of the 158 patients with normal serum sodium levels developed at least one hyponatremic episode during ICU treatment. The number of hyponatremic episodes was similar between patients with higher-grade and lower-grade aneurysmal SAH (P = 0.848). At the end of ICU treatment, outcome did not differ between patients with and without hyponatremia (40/88, 45.5% vs. 38/70, 54.3%, P = 0.270). At 6 months after SAH, however, good outcome (Glasgow outcome scale, GOS 4–5) was more frequently observed in patients with hyponatremia (26/88, 29.5% vs. 32/70, 45.7%, P = 0.036). Medication with sodium chloride, fludrocortisone, or tolvaptan was initiated in 75.4% patients with mild hyponatremia (130–134 mmol/L) and in 92.9% with moderate hyponatremia (125–129 mmol/L). At 6 months after SAH, patients treated with tolvaptan had a lower rate of poor outcome than patients who had not received tolvaptan (1/14, 7.1% vs. 25/74, 33.8%, P = 0.045). In patients with acute aneurysmal SAH and hyponatremic episodes, consequent treatment of hyponatremia prevented impaired outcome. Because administration of tolvaptan rapidly normalized serum sodium levels, this therapy seems to be a promising treatment approach.     

复方丹参滴丸联合托伐普坦治疗急性心肌梗死并发心力衰竭的临床研究

目的探讨复方丹参滴丸联合托伐普坦治疗急性心肌梗死并发心力衰竭的临床效果。方法选取2018年3月-2019年8月新乡医学院第一附属医院收治的94例急性心肌梗死并发心力衰竭患者,随机分成对照组(47例)和治疗组(47例)。对照组口服托伐普坦片,15 mg/次,1次/d。治疗组在对照组基础上口服复方丹参滴丸,0.27 g/次,3次/d。两组均治疗7 d。观察两组患者临床疗效,比较治疗前后两组患者24h尿量、临床表现缓解时间,心脏标志物心肌肌钙蛋白I(cTnI)、肌红蛋白(Myo)、心脏脂肪酸结合蛋白(H-FABP)、B型利钠肽(BNP)和半乳糖凝集素-3(Gal-3)水平及超声心动图参数。结果治疗后,对照组和治疗组临床有效率分别为78.7%、93.6%,两组比较差异有统计学意义(P<0.05)。治疗后,治疗组24 h尿量显著增加(P<0.05),且治疗组相关临床表现缓解时间则均比对照组显著缩短(P<0.05)。治疗后,两组患者血清cTnI、Myo、H-FABP、BNP和Gal-3水平显著低于治疗前(P<0.05),且治疗组患者比对照组下降更为显著(P<0.05)。治疗后,两组患者左室射血分数(LVEF)、心排量(CO)均显著高于治疗前(P<0.05),而左心房容积指数(LAVI)、二尖瓣口舒张早期血流速度峰值与二尖瓣环舒张早期组织运动速度峰值比值(E/e’)均显著降低(P<0.05),且治疗组这些超声心动图参数显著优于对照组(P<0.05)。结论复方丹参滴丸联合托伐普坦能有效缩短急性心肌梗死并发心力衰竭患者临床症状的持续时间,减轻心脏损伤,并有助于促进病人心脏结构及功能的恢复,疗效确切,安全可靠。     

托伐普坦片治疗肝硬化腹水低钠血症的疗效及安全性观察

目的:观察托伐普坦片治疗肝硬化腹水引起的低钠血症患者的疗效及安全性。方法:40例肝硬化伴腹水形成的低钠血症患者,予以口服托伐普坦片治疗。结果:口服托伐普坦片治疗肝硬化腹水低钠血症明显优于安慰剂组(P<0.05)。结论:托伐普坦片能够明显提高肝硬化患者血清钠浓度作用,对低钠血症患者有明显疗效。没有严重并发症及不良反应,临床应用中简便且安全。     

左西孟旦联合托伐普坦治疗急性心力衰竭的疗效研究

目的研究分析左西孟旦联合托伐普坦治疗急性心力衰竭的疗效。方法选取我院2016年8月-2019年1月确诊并治疗的急性心力衰竭患者102例,随机分为对照组观察组各51例。给予对照组左西孟旦治疗,观察组则在对照组的基础上联合托伐普坦进行治疗,对两组患者的心率、收缩压、射血分数及24 h尿量进行比较。结果治疗后,观察组心率、收缩压低于对照组,EF及24 h尿量高于对照组,差异有统计学意义(P<0.05);治疗后观察组心功能改善有效率明显优于对照组,差异有统计学意义(P<0.05)。结论在急性心力衰竭的临床治疗上,观察组心率、收缩压低于对照组,射血分数及24 h尿量高于对照组。     

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.     

Efficacy of Long‐Term Treatment With Tolvaptan to Prolong the Time Until Dialysis Initiation in Patients With Chronic Kidney Disease and Heart Failure

The short‐term effectiveness of tolvaptan (TLV) against heart failure has been established. TLV is known to decrease the worsening of renal function more than loop diuretics. Long‐term TLV administration decreases the rate of re‐hospitalization in heart failure and prevents deterioration of kidney function. If repeated hospitalization for heart failure can be prevented in patients having concurrent chronic kidney disease (CKD), the period until dialysis initiation may be prolonged. We investigated whether long‐term TLV management can extend the period until dialysis initiation in patients with CKD and heart failure. A retrospective, observational study was conducted among patients with CKD stage G4 and G5 admitted because of heart failure between April 2013 and July 2018. They were divided into those with TLV and those without TLV. They were followed up until August 2018 and relevant data was collected. Data from 115 patients (68 men and 47 women), with a mean age of 73.4 ± 11.9 (median 76.0 and IQR 66.5–82.0) years and a mean eGFR of 11.8 ± 5.7 (median 9.9 and IQR 7.5–14.8) mL/min/1.73m² were included in the analysis. Twenty‐five patients had received long‐term TLV treatment, and 90 had not. Multivariate analysis after adjustment showed that long‐term use of TLV significantly lowered the hazard ratio (HR) for time taken to reach dialysis initiation (HR: 0.3286, 95%CI: 0.1282–0.8423, P = 0.0205). Propensity score‐matched analysis showed similar results (HR: 0.3220, 95%CI: 0.1107–0.9369, P = 0.0376). In patients with CKD G4 and G5 and heart failure, long‐term treatment with TLV can prolong the time until dialysis initiation.     

托伐普坦片在中国健康人体的生物等效性研究

目的：评价试验制剂托伐普坦片与参比制剂托伐普坦片在中国健康人体中的生物等效性。方法：采用双周期随机交叉试验设计,入选24名男性健康受试者单次口服参比制剂和试验制剂30mg,采用高效液相色谱-串联质谱法（HPLC—MS／MS）测定血浆中托伐普坦的浓度,经DAS2．1软件处理参数,并进行双单侧t检验确定是否等效。结果：试验制剂和参比制剂的主要药代动力学参数分别为：cmax为（179±97）和（189±86）μg／L;tmax为（2．5±1．1）和（2．5±1．0）h;AUC0-t为（1153±488）和（1225±528）μg·h·L-1;AUC0。。为（1161±492）和（1232±528）μg·h·L-1;t1／2为（5．6±2．0）和（5．6±2．0）h。试验制剂对参比制剂的相对生物利用度F为（95．8±18．7）％。结论：试验制剂托伐普坦片与参比制剂托伐普坦片生物等效。     

托伐普坦治疗肝硬化低钠血症研究进展

托伐普坦是一种新型非肽类选择性血管精氨酸加压素V2受体拮抗剂,具有增加肾脏自由水排出、提高血清钠浓度的作用。因失代偿期肝硬化患者自由水排出障碍而常常致低钠血症。应用托伐普坦治疗肝硬化低钠血症可以有效地增加血钠浓度,减少肝性脑病、肝肾综合症、顽固性腹水等并发症的发生。本文简要概述了托伐普坦的作用机制,并介绍了其治疗肝硬化低钠血症的有效性及安全性,以更好地指导临床应用。     

托伐普坦治疗充血性心力衰竭的疗效和安全性评价——meta分析

目的:评价托伐普坦对充血性心力衰竭的治疗效果及安全性。方法:通过检索Pubmed、中国生物医学文献等数据库,手工检索已纳入的相关文献,对符合随机对照条件的研究经质量评估、数据提取,进行meta分析。结果:纳入10项随机、双盲、安慰剂对照研究。共计5 086例病例,4 958例完成研究设计随访。Meta分析结果显示,治疗组体质量(单位:0.1 kg)减轻[加权均数差(WMD)=-8.29,95%CI:-9.38~-7.20,P0.001],尿量(单位:100 mL)增加(WMD=14.58,95%CI:8.22~20.95,P0.001),血钠(单位:mmol/L)增加(WMD=2.83,95%CI:1.66~4.01,P0.01);与安慰剂比较,长期治疗的主要不良反应为口渴、口干和尿频;亚组分析显示,短期(1周)治疗,不良事件发生率无明显增加(WMD=1.35,95%CI:0.61~2.97,P=0.46)。托伐普坦对死亡率和再住院率无明显影响。结论:充血性心力衰竭患者选择性使用托伐普坦(30 mg/d)可以减轻体液潴留、纠正低钠血症,长期用药可能出现口渴、口干和尿频。     

Efficacy of tolvaptan in patients with refractory ascites in a clinical setting

AIM: To elucidate the efficacies of tolvaptan (TLV) as a treatment for refractory ascites compared with conventional treatment.METHODS: We retrospectively enrolled 120 refractory ascites patients between January 1, 2009 and September 31, 2014. Sixty patients were treated with oral TLV at a starting dose of 3.75 mg/d in addition to sodium restriction (> 7 g/d), albumin infusion (10-20 g/wk), and standard diuretic therapy (20-60 mg/d furosemide and 25-50 mg/d spironolactone) and 60 patients with large volume paracentesis in addition to sodium restriction (less than 7 g/d), albumin infusion (10-20 g/wk), and standard diuretic therapy (20-120 mg/d furosemide and 25-150 mg/d spironolactone). Patient demographics and laboratory data, including liver function, were not matched due to the small number of patients. Continuous variables were analyzed by unpaired t-test or paired t-test. Fisher’s exact test was applied in cases comparing two nominal variables. We analyzed factors affecting clinical outcomes using receiver operating characteristic curves and multivariate regression analysis. We also used multivariate Cox’s proportional hazard regression analysis to elucidate the risk factors that contributed to the increased incidence of ascites.RESULTS: TLV was effective in 38 (63.3%) patients. The best cut-off values for urine output and reduced urine osmolality as measures of refractory ascites improvement were > 1800 mL within the first 24 h and > 30%, respectively. Multivariate regression analysis indicated that > 25% reduced urine osmolality [odds ratio (OR) = 20.7; P < 0.01] and positive hepatitis C viral antibodies (OR = 5.93; P = 0.05) were positively correlated with an improvement of refractory ascites, while the total bilirubin level per 1.0 mg/dL (OR = 0.57; P = 0.02) was negatively correlated with improvement. In comparing the TLV group and controls, only the serum sodium level was significantly lower in the TLV group (133 mEq/L vs 136 mEq/L; P = 0.02). However, there were no significant differences in the other parameters between the two groups. The cumulative incidence rate was significantly higher in the control group with a median incidence time of 30 d in the TLV group and 20 d in the control group (P = 0.01). Cox hazard proportional multivariate analysis indicated that the use of TLV (OR = 0.58; P < 0.01), uncontrolled liver neoplasms (OR = 1.92; P < 0.01), total bilirubin level per 1.0 mg/dL (OR = 1.10; P < 0.01), and higher sodium level per 1.0 mEq/L (OR = 0.94; P < 0.01) were independent factors that contributed to incidence.CONCLUSION: Administration of TLV results in better control of refractory ascites and reduced the incidence of additional invasive procedures or hospitalization compared with conventional ascites treatments.