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1、1心力衰竭治疗中的难点钠水潴留水电解质紊乱利尿剂稀释性低钠难治性心衰恶性心律失常第1页/共35页2主要内容心力衰竭-钠水潴留的原因利尿剂应用与电解质紊乱纠正低钠血症及电解质紊乱策略第2页/共35页3主要参考文献2013 ACCF/AHA Guideline for the Management of Heart FailureESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012第3页/共35页4心力衰竭-钠水潴留的原因心衰早期，RAAS系统激活:1.循环血液重新分配，2.维持
2、重要器官动脉血压和血流灌注。心衰晚期,RAAS持续及过度激活:1.水钠过度潴留,电解质紊乱,及心律失常.2.外周血管痉挛,使心脏前后负荷增加 3.导致心功能进一步恶化，最终形成难治性心力衰竭。第4页/共35页5心力衰竭-钠水潴留的原因低钠血症-AVP系统(精氨酸加压素arginine vasopressin，AVP):1.RAAS刺激垂体后叶分泌AVP,使肾远曲小管和髓质集合管对水的重吸收增加；2.Ag增加近曲小管钠转运，至远曲小管和集合管钠转运减少。4.RAAS总的效应是体内水和钠的含量均增加，但水的含量增加更明显，造成高容量性稀释性低钠血症。第5页/共35页6心力衰竭-钠水潴留的原因心衰晚
3、期低钠血症-BNP 系统:1.心力衰竭时,RAAS持续恶化，心室容量超负荷及室壁张力改变的刺激，使BNP的表达、分泌和活性增加。2.BNP直接作用于肾小球和集合管，抑制肾素的释放和醛固酮的分泌，增加尿钠和尿液的排泌，使血钠下降，能诱导血容量减少性低钠血症。第6页/共35页7心力衰竭-电解质紊乱原因心力衰竭患者因胃肠瘀血，恶心、呕吐，使血清钠、钾排泄过多，造成低钾、低钠血症。心力衰竭时强调限盐，是血钠、钾等电解质摄人不足的重要因素。老年人肾脏储备功能下降，肾小管对钠、钾的重吸收减少。摄人不足与排泄过多第7页/共35页8主要内容心力衰竭-钠水潴留的原因利尿剂应用与电解质紊乱纠正低钠血症的策略与方法
4、第8页/共35页9心力衰竭的治疗-利尿剂的应用第9页/共35页10利利 尿尿 剂剂起起 始始 剂剂 量量(mg)(mg)每日常用剂量每日常用剂量(mg)(mg)袢袢 利利 尿尿 剂剂a a呋塞米呋塞米202040404040240240布美他尼布美他尼0.50.51.01.01 15 5托拉噻米托拉噻米5 5101010102020噻嗪类噻嗪类b b苄氟噻嗪苄氟噻嗪2.52.52.52.51010氢氯噻嗪氢氯噻嗪 252512.512.5100100美托拉宗美托拉宗2.52.52.52.51010吲哒帕胺吲哒帕胺c c2.52.52.52.55 5保钾利尿剂保钾利尿剂d d+ACEi/+ACE
5、i/ARB ARB -ACEi/ARB-ACEi/ARB+ACEi/AR+ACEi/ARB B-ACEi/ARB-ACEi/ARB螺内酯螺内酯/依普利酮依普利酮12.512.5252550505050100100200200阿米洛利阿米洛利2.52.55 55 5101010102020氨苯喋啶氨苯喋啶25255050100100200200A A：口服或静脉注射，根据容量状态/体重，剂量可能需要调整，过量可引起肾损害或耳毒性；B B：如果估算的肾小球滤过率30 mL/min1.52.0kg持续2天，则增加利尿剂剂量。McMurrayJJ,AdamopoulosS,AnkerSD,etal.E
6、SCGuidelinesforthediagnosisandtreatmentofacuteandchronicheartfailure2012.EuropeanHeartJournal(2012)33,17871847利尿剂的选择第11页/共35页12Stages,Phenotypes and Treatment of HF第12页/共35页13Pharmacologic Treatment for Stage C HFrEF第13页/共35页14Pharmacological Treatment for Stage C HFrEF(cont.)Diuretics are recommend
7、ed in patients with HFrEF who have evidence of fluid retention,unless contraindicated,to improve symptoms.ACE inhibitors are recommended in patients with HFrEF and current or prior symptoms,unless contraindicated,to reduce morbidity and mortality.ARBs are recommended in patients with HFrEF with curr
8、ent or prior symptoms who are ACE inhibitor-intolerant,unless contraindicated,to reduce morbidity and mortality.I IIa IIb IIII IIa IIb IIII IIa IIb III第14页/共35页15Pharmacological Treatment for Stage C HFrEF(cont.)1.Aldosterone receptor antagonists or mineralocorticoid receptor antagonists(MRA)are rec
9、ommended in patients with NYHA class II-IV and who have LVEF of 35%or less,2.Creatinine should be 2.5 mg/dL or less in men or 2.0 mg/dL or less in women(or estimated glomerular filtration rate 30 mL/min/1.73m2)and potassium should be less than 5.0 mEq/L.3.Careful monitoring of potassium,renal functi
10、on,to minimize risk of hyperkalemia and renal insufficiency.I IIa IIb III第15页/共35页16Pharmacological Treatment for Stage C HFrEF(cont.)Aldosterone receptor antagonists are recommended to reduce morbidity and mortality following an acute MI in patients who have LVEF of 40%or less who develop symptoms
11、of HF or who have a history of diabetes mellitus,unless contraindicated.1.Inappropriate use of aldosterone receptor antagonists is potentially harmful 2.serum creatinine greater than 2.5 mg/dL in men or greater than 2.0 mg/dL in women(or estimated glomerular filtration rate 30 mL/min/1.73m2),and/or
12、potassium above 5.0 mEq/L.I IIa IIb IIII IIa IIb IIIHarm第16页/共35页17Pharmacological Treatment for Stage C HFpEF Systolic and diastolic blood pressure should be controlled in patients with HFpEF in accordance with published clinical practice guidelines to prevent morbidity.Diuretics should be used for
13、 relief of symptoms due to volume overload in patients with HFpEF.Coronary revascularization is reasonable in patients with CAD in whom symptoms(angina)or demonstrable myocardial ischemia is judged to be having an adverse effect on symptomatic HFpEF despite GDMT.I IIa IIb IIII IIa IIb IIII IIa IIb I
14、II第17页/共35页18利尿剂应用与电解质紊乱利尿剂：利尿药是心力衰竭的基础用药。但无论是噻嗪类利尿剂还是袢利尿剂，长期或大剂量使用均能增加血清钠、钾排出，导致低钠、低钾血症。而且还能使有效血容量减少，也可进一步刺激AVP分泌增加。螺内酯等保钾利尿剂单独或与ACEI类药物联合应用则易致高钾血症。药物对电解质的影响第18页/共35页19主要内容心力衰竭-钠水潴留的原因利尿剂应用与电解质紊乱纠正低钠血症及电解质紊乱策略第19页/共35页20纠正低钠血症及电解质紊乱策略异常异常原因原因临床意义临床意义低钠血症低钠血症(150 mmol/L)水丢失水丢失/水摄入不足水摄入不足评估水摄入、诊断性检查评
15、估水摄入、诊断性检查低钾血症低钾血症(5.5 mmol/L)肾衰、补钾、肾衰、补钾、RAS抑制剂抑制剂停止补钾停止补钾/保钾利尿剂、保钾利尿剂、减量减量/停止停止ACEI/ARB、MRA、评估肾功和尿、评估肾功和尿pH、心动过缓和严重心律失、心动过缓和严重心律失常的危险常的危险McMurrayJJ,AdamopoulosS,AnkerSD,etal.ESCGuidelinesforthediagnosisandtreatmentofacuteandchronicheartfailure2012.EuropeanHeartJournal(2012)33,17871847第20页/共35页21纠正
16、低钠血症及电解质紊乱策略AVP受体拮抗药1.常用的AVP受体拮抗剂有托伐普坦、利希普坦、考尼伐坦等，其问世是伴有低钠血症的心力衰竭治疗的最重大的进展。2.AVP受体拮抗药可抑制AVP的过量分泌，在不改变钠、钾排泄的情况下产生利尿作用，促进自由水的排泄，维持钠和其他电解质的浓度，被称为排水利尿剂。3.该药增加液体丢失，降低尿渗透压，它们不激活RAAS，因此不引起低渗性低钠血症或血压升高。第21页/共35页22Arginine Vasopressin AntagonistsIn patients hospitalized with volume overload,including HF,who
17、have persistent severe hyponatremia and are at risk for or having active cognitive symptoms despite water restriction and maximization of GDMT,vasopressin antagonists may be considered in the short term to improve serum sodium concentration in hypervolemic,hyponatremic states with either a V2 recept
18、or selective or a nonselective vasopressin antagonist.I IIa IIb III第22页/共35页23纠正低钠血症及电解质紊乱策略老年CHF患者常为稀释性低钠血症，发生机制多为钠摄入低于钠排出和(或)水潴留大于钠潴留，与长期严格限盐而未限水有关，多见于心功能进行性恶化者。过度限盐不仅无助于心力衰竭的纠正，反而会因低钠血症的发生加快心力衰竭的发展。不需大量、长期利尿治疗(多为病史短的心功能I级)者，可以适当限盐，以利水钠潴留的防治；对需要长期、大量利尿治疗(多为病史长的心功能级)者，则不限制经饮食途径摄入的盐的量，并根据血钠水平检测，适时适当
19、地补盐，以避免低钠血症的发生。第23页/共35页24Water RestrictionFluid restriction(1.5 to 2 L/d)is reasonable in stage D,especially in patients with hyponatremia,to reduce congestive symptoms.I IIa IIb III第24页/共35页25纠正低钠血症的策略与方法低钠血症 容量耗竭：停用噻嗪类或转换到袢利尿剂；如果可能减量/停用 袢利尿剂。容量负荷过重：限制液体；袢利尿剂加量；考虑AVP剂（如能得到用托伐普坦）；静脉正性肌力药支持；考虑超滤。Hyp
20、onatraemiaVolume depleted:stop thiazide or switch to loop diuretic,if possible;reduce dose/stop loop diuretics if possible;volume overloaded:fluid restriction;increase dose of loop diuretic;consider AVP antagonist(e.g.tolvaptan if available);i.v.inotropic support;consider ultrafiltrationMcMurrayJJ,A
21、damopoulosS,AnkerSD,etal.ESCGuidelinesforthediagnosisandtreatmentofacuteandchronicheartfailure2012.EuropeanHeartJournal(2012)33,17871847第25页/共35页26纠正低钾血症的策略与方法保钾利尿剂的使用和补钾 如果排钾利尿剂与ACEI和MRA（或ARB）联用，通常不需要补钾。除了ACEI（ARB）与MRA联用外，或补钾可能不需要。不推荐ACEI、MRA和ARB 三类药物全用 Use of potassium-sparing diuretics and potass
22、ium supplementsIf a potassium-losing diuretic is used with the combination of an ACE inhibitor and an MRA(or ARB),potassium replacement is usually not required.Serious hyperkalaemia may occur if potassium-sparing diuretics or supplements are taken in addition to the combination of an ACE inhibitor(o
23、r ARB)and MRA.The use of all three of an ACE inhibitor,MRA and ARB is not recommended.McMurrayJJ,AdamopoulosS,AnkerSD,etal.ESCGuidelinesforthediagnosisandtreatmentofacuteandchronicheartfailure2012.EuropeanHeartJournal(2012)33,17871847第26页/共35页27纠正低钾血症的策略与方法Initial laboratory evaluation of patients p
24、resenting with HF should include complete blood count,urinalysis,serum electrolytes(including calcium and magnesium),blood urea nitrogen,serum creatinine,glucose,fasting lipid profile,liver function tests,and thyroid-stimulating hormone.Serial monitoring,when indicated,should include serum electroly
25、tes and renal function.I IIa IIb IIII IIa IIb III第27页/共35页28利尿剂应用的适应症及禁忌症McMurrayJJ,AdamopoulosS,AnkerSD,etal.ESCGuidelinesforthediagnosisandtreatmentofacuteandchronicheartfailure2012.EuropeanHeartJournal(2012)33,17871847适应症1.充血症状和体征的患者，无论EF如何；2.EF降低者，与ACEI（或ARB）、-阻滞剂和MRA联用；最小剂以维持正常血容量“干重”（即保持无充血的症状
26、和体征的重量)；剂量根据患者的容量状态增减；禁忌症1.如果患者没有充血的症状或体征就没有适应症;2.已知的过敏反应。其它不良反应（药物-特异的）第28页/共35页29利尿剂应用的注意事项McMurrayJJ,AdamopoulosS,AnkerSD,etal.ESCGuidelinesforthediagnosisandtreatmentofacuteandchronicheartfailure2012.EuropeanHeartJournal(2012)33,178718471.明显的低钾血症(K+3.5mmol/L)利尿剂可能会雪上加霜;2.肾损害(肌酐150mol/L/1.7mg/dL,
27、eGFR221mol/L(2.5mg/dL)或eGFR30mL/min/1.73m2)噻嗪类利尿剂可加重肾功能损害或患者可能对利尿剂无效;4.症状性或重度无症状性低血压（收缩压150mol/L/1.7mg/dL,eGFR221mol/L(2.5mg/dL)或eGFR30mL/min/1.73m2)噻嗪类利尿剂可加重肾功能损害;4.症状性或重度无症状性低血压（收缩压90mmHg)可因利尿剂所致加重低血容量;5.螺内酯和依普利酮可引起高钾血症和肾功能恶化，如果用了二者之一，需要连续监测血电解质和肾功能第29页/共35页30利尿剂应用注意事项检查肾功能和电解质:1.以小剂量开始；2.在启动治疗和任何
28、加量后1-2周复查血液生化（BUN、肌酐、K+）3.当停止加量、减量、停止治疗时要复查；4.一个专科心衰护士可协助患者教育、随访（当面或电话）、生化监测和剂量调整（包括训练患者调整剂量）。McMurrayJJ,AdamopoulosS,AnkerSD,etal.ESCGuidelinesforthediagnosisandtreatmentofacuteandchronicheartfailure2012.EuropeanHeartJournal(2012)33,17871847第30页/共35页31利尿剂与药物的相互反应注意药物相互反应 1.与ACEI或ARB或肾素抑制剂联用低血压危险 2.
29、与其它利尿剂（如袢利尿剂加噻嗪类）低血容量、低血压、低血钾和肾损害的危险 3.NSAIDs 可减弱利尿作用。McMurray JJ,Adamopoulos S,Anker SD,et al.ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012.European Heart Journal(2012)33,17871847第31页/共35页32纠正电解质紊乱低钾血症 ACEI/ARB加量、加用MRA、补钾低钠血症 容量不足：停用噻嗪类或转换到袢利尿剂；或减量/停用袢利尿剂；容量
30、负荷过重：限制液体；袢利尿剂加量；考虑AVP剂（如能得到用托伐普坦）；静脉正性肌力药支持；考虑超滤。McMurrayJJ,AdamopoulosS,AnkerSD,etal.ESCGuidelinesforthediagnosisandtreatmentofacuteandchronicheartfailure2012.EuropeanHeartJournal(2012)33,17871847第32页/共35页33小结1.心力衰竭时神经内分泌系统激活与钠水潴留电解质紊乱密切相关.2.利尿剂是GDMT重要的治疗药物3.水电解质平衡在心力衰竭管理重要第33页/共35页34 谢谢第34页/共35页35感谢您的观看！第35页/共35页