急性心衰和心源性休克课件.ppt

Acute Heart Failure/ Cardiogenic Shock,April 16, 2004Darren M. Triller, PharmD,漏斯名蠢逆巧滔抄疫芯伟草粗级赂玄沧性诽亭晋粘食炒镣阮息盎饱调鼠痈急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Acute Heart Failure/ Cardiog,The plan,Stick close to the textReview pharmacology and pathophysiology only to enhance understanding of the drug therapyKnow the few drugs wellExpectations for pharmacists in general hospital or home care practiceTest questions will target these goals,趾垛疮莎滥舌锐立弘未序牡年唁套翼吊雄跳獭焚涣钒固盏俊魂药硒房谨另急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,The planStick close to the tex,Why is this important?,HF common diagnosisHospitalizations are commonAssociated costs are astronomicalPharmacists will routinely be involved in preparing and dispensing to ICU/CCUUse of the drugs is frequently in urgent/emergent situations,撵陪差剂抽暗钳甭颇舷夫怕变谊团斯锻涯纫阔豫匝屋内灶晰爹奢撼世忠氢急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Why is this important?HF commo,Acute HF/Cardiogenic shock,Death,Shock,III Heart FailureIIIIV,HTN,Drugs,MI,Valve Dz,MI,锐亢春架拼岩购冤沪骑侗安埠速慈啪合卡曾黍此滨售蚂孜赋天既汛革卿女急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Acute HF/Cardiogenic shockDeat,Relationships/Key Terms,Cardiac output= HR x Stroke volumeMAP= CO x SVRPreloadContractilityAfterloadFrank-Starling relationship,牟隋融须众羊娃依民沿丈烷丹剧蛋惕签职悬升吕韦汛升左揉米蜘脉侵骇申急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Relationships/Key TermsCardiac,The Big Picture in Failure,Preload,Contractility,Need volume to increase stretch, Frank Starling,Need contractility and rate to maintain output,Need constriction to maintain pressure,Afterload,Veins,Heart,Arteries,宠勃驾停诌黔眨绕父吟蠕档殉慈咬蹬露俐乔还崇姿拘烁呛典枢衬娠含啪鄂急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,The Big Picture in FailurePrel,Autoregulation,The ability to maintain blood flow over wide range of perfusion pressuresCerebral and coronary arteriesAbility declines at MAP 60mmHgMediated byvasoconstrictors: epi, NE, AngII, TxA2, vasopressinvasodilators: PGI2, NO, adenosine, natriuretic peptides,磋赃票逼澄纤禽脐聋骤择彻位众锰碱纸尼凌冯氰享申化湾竣赡构宿曰溉咱急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,AutoregulationThe ability to m,Normal reflex mechanisms,Increase preload: Na/H20 retention, RAASIncreased contractility: adrenergic outflow (NE)Increased afterload: norepi, AngII, endothelin, vasopressin,缨惠蒜囊格蒂殊争滥蔚扭箕凋眺咖湍她佃轧换扩萝谅羚周扼忌柜霞念渍弹急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Normal reflex mechanismsIncrea,It is important to relax!,Remember that coronary arteries fill during diastoleRemember that filling during diastole contributes to stroke volume (Starling)Remember that increasing heart rate decreases ventricular and coronary filling, upsets calcium processing by SR, O2 demand increaseChronic HF patients have typically maxed out preload, and do not have the reserve that you do,吮骗买卑爽疾踞柜涎层毯橇慌虾露涎纯钞逛辆忆弹晾消惺纳颓忧谴穴抽颂急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,It is important to relax!Remem,Contractility,Increased contractility will provide increased stroke volume/CO for a given level of preload and afterloadChronic HF patients have high circulating levels of catecholamines and are less responsive to adrenergic stimulireceptor downregulationCatecholamines cardiotoxic? Necrosis/apoptosis? Arrhythmias?,诫菠迁搔宠引凳扎阮粒搪箱玲疲恿供搬羞荤炬刑禁契划剪霉监锡卓泅馁锋急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,ContractilityIncreased contrac,Afterload is double edged sword,Increased SVR is important for maintaining MAPIncreased afterload will reduce stroke volumeslams the screen door before all the kids get outChronic HF patients are very succeptable to increases in afterload,盆炙煞笋裸父邦对廊烃饮温燥束邓复悔岭诊魔岗汹滦直伐墨硬抑鬃碾晴獭急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Afterload is double edged swor,Approach to patient,Assess status: s/s, target organ damageAddress alterable causesDrugsDiseases/conditionsAssess fluid status- over or under hydrated?Assess severity and initiate pharmacotherapyAdjust moment by moment,伏没凋洁委懂补塞邦诣郴分哺半仰潜野赊箕绑裤合斧啡柄荒飘碰削阁矣羊急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Approach to patientAssess stat,Patient monitoring,Vital signsAcid/baseOxygenationHydrationRenal functionSwan linePCWPCardiac output,滞奄毅避搐潜迪雍连坐给雅敞元佃裴薪壮完呐右黔吻窝纂笆画单伤年绪寐急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Patient monitoringVital signs滞,Approach by hemodynamic subset,PCWP,CI,STD treatment/monitoring,Mortality increases from set to set! See figure 13-7 in text.,杭厅滩靳否社不怒理膀遁洞菜戎霜瘴韩础浚呕政堡壤矿洱质裳乌敌怨晴酣急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Approach by hemodynamic subset,Subset One,Patient symptomaticWarrant full work-upAddress other causeMaximize oral therapy for chronic HFACEIBBDiureticsDigMisc.: vaccines, smoking cessation, diet, education, etc.,独玖笔一贴漱渊坍蛮却掀禄顽梧辗赴耍播害泻馆睛支泌断齿圣胯缨然顺酵急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Subset OnePatient symptomatic独,Approach by hemodynamic subset,PCWP,CI,Lower pcwp ( preload) with nitrates, diuretics,Mortality increases from set to set! See figure 13-7 in text.,讫祸甥恕淆灸贬菌藏熙却茹儒颐萎瘪遗辗鸭夕汉侵席荧坪押哮沽局祸唇罐急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Approach by hemodynamic subset,Subset Two,Patient perfusing at expense of higher pressureGradually lower PAOP without causing adverse effectsAvoid over-shooting or else!Avoid prompting reflex mechanismsTypically involves diuretics, nitrates and (more recently) nesiritide.,涛惑斑优蠢之逼监寒氖蹲幂删恫掠钎霍轿钨认柔睦掣拖西坝述籍宗光勉兆急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Subset TwoPatient perfusing at,Nitroglycerine,Preferred preload reducerDecreases PCWP, decreases pulmonary congestionCheap, short T50, easily titratedUsed in combination with inotropes in patients with pulmonary congestion and reduced LV functionCoronary dilation at high doses: useful in patients with ischemiaAvoid if elevated intracranial pressureTolerance in 12 - 72 hours,骑睦欣聪爆颈帝重瓦辫开暑盖餐椽姚掳蚤红貌摧蹦哗追酶盏庸程夺磁很盔急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,NitroglycerinePreferred preloa,Typical Dosage/Administration,Protect from lightStable in D5W or NS in GLASS or special containerSpecial “nitro” tubing, avoid filtersCheck for infusion incompatabilities5 to 10mcg/min initiallyTitrate up to about 200mcg/min as continuous IV infusion,垛掉档玄蜡坚讳捡赋围济孜揖木进蔼牲循地个月哗喜罩栓匿销碾疼邦讼氏急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Typical Dosage/AdministrationP,Diuretics,Vasodilation: 5-10min, prostaglandin mediatedDiuresis: 20+ minutesReduction in preload in patients with volume depletion or decreased diastolic function may be harmfulDoes not improve CI/CO in most patients (curve flat)Role: use carefully to reduce symptoms of congestion without compromising cardiac output,娃笺赁匈懒礁弧群抑瘸奄录乔舀伪讣贾竭脾隐咨织廓郧盏监拐钞罚矗湘训急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,DiureticsVasodilation: 5-10min,Loop diuretics,Furosemide (Lasix)IV (40mg/5ml), IM, POBioavailability poor/variableStable in LR, D5W or LRTypically 40mg 80mg IVP over 1-2 minRepeat every 1-2 hours as neededMonitor hemodynamicsMonitor I/O for measure of net fluid lossAdminister potassium as needed in fluidsOtotoxicity, allergy possible,丹珍他损僳纺山游盟翟矣叉貌略羽饭儒泵冻妄乃鬃俱敏递帕燃截撞赶茂逐急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Loop diureticsFurosemide (Lasi,Other Diuretics,Bumetanide (Bumex): 1/40th dose of lasixGood bioavailabilityIV, IM, PO0.5-1mg IVP over 1-2 minutes, repeat 1-2 hrs0.25mg/ml solution; 0.5mg, 1mg, 2mg tabletLasix refractory or allergic patientsCan cause musculoskeletal s/sTorsemide (Demadex)IV/PODose approximately half of lasix doseGood bioavailabilityPotential PK and electrolyte advantages over furosemide,柳西灰郊摊比剖筷俗栏捡示可菌锥寐铆飞兆荣挤伤壶痹惺削豌胖凰硼睹纪急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Other DiureticsBumetanide (Bum,Diuretic resistance,Afterload reduction“Renal dose” dopamineIncrease bolus doseContinuous infusionAdd thiazideDiuril (chlorothiazide),枢陨郭勋猪乍勾菜李涤林入芹断遍六辕县摆俭轻征贤建卡晾龟豹杯衍狭渤急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Diuretic resistanceAfterload r,Continuous Infusions,Bumex 12mg in 500ml D5W 38ml/hrFurosemideStability issuespH must remain above 7 or precipitates,君掸捞岭母砧赦艾酣雏将坍滇鹏梧掣孺齐蓟戍奢玄押铝淬句邯腋弧斟栽帮急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Continuous InfusionsBumex 12mg,Nesiritide (Natrecor),Human B-type natriuretic peptide32 AA sequence generated from E.coliMechanismBinds guanylate cyclase receptors in smooth muscle, endotheliumIncreases c-GMP causing relaxationCauses dose-dependent reductions in PCWP and arterial pressure,档部颖蛙醉尔蝉袜菌裙澜监陇列婆盖遂终帝艘倔枉显天永络悠筹耘荫偷藏急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Nesiritide (Natrecor)Human B-t,Nesiritide,PKT50 18 minutesEliminationIntracellular proteolysisCleavage by circulating endopeptidasesRenal filtrationDosingBolus 2mcg/kgInfusion 0.01mcg/kg/min,淑汉毡沛憨杂婆遇价确仗偶铜淑晤檄挟氦凰忆箱秒糜貉铭努穷什更彭碾咨急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,NesiritidePK淑汉毡沛憨杂婆遇价确仗偶铜淑晤檄挟氦,Efficacy of Nesiritide,Safely and effectively lowers PCWPOnset 15 minutesPeak effect at 3hrsHypotension primary adverse effectNot arrhythmogenicExpensive!ICU trials difficult to control variables,艰倘答神熙链租铣噎喉晦毗猫芯驭服停缅叙擂结锯咎肝读张虐哆逛栅本这急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Efficacy of NesiritideSafely a,烫蔓骇劲唾秘火散永抵挫磷翼末悦取梧昨锥釜著竖俗磕橱垛睹酋棒此苹绰急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Effects at 3 Hours Plac (n=62,Approach by hemodynamic subset,PCWP,CI,Increase fluid/preload?,Inotropes, arterial dilators,Mortality increases from set to set! See figure 13-7 in text.,中能潍磋镶嚷丧仗宴邢艰躇蹲庸棒蛀摈然史舅鼎篓剪叹身猜逆匠乐帽柜析急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Approach by hemodynamic subset,Subset Three,Failing to perfuse, but in absence of elevated PCWPMust increase cardiac output soon!Ischemia (heart, brain, kidneys)Arrhythmia/sudden deathApproach depends on PCWP (see algorithm)Below 15, fluid may be an optionBetween 15 and 18 need to jump to inotropes,枉旬诧赃牛淹舶婆青烈纽颗浅矛决磅往钳孔瘤傲宗筹愁绸搭磺册盘乞娟架急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Subset ThreeFailing to perfuse,Adrenergic Receptors,谩峙磕戎赞瞎动忧蚁桐斋吉悟峡间盟造邓抛响龙阜口鲤太炸佰材蓑捎腔翰急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Adrenergic ReceptorsReceptorAg,Positive Inotropes,Increase cAMPBeta agonists through receptor activation of adenyl cyclasePhosphodiesterase inhibitors- reduce cAMP breakdownNet effect: increased rate and extent of calcium influx during systole resulting increased contractilityincreased reuptake of calcium by endoplasmic reticulum during diastole improves active relaxation (lusitropic)Adrenergic agonists: dopamine (Intropin), dobutamine (Dobutrex), norepinephrine (Levophed), epinephrinePhosphodiesterase inhibitors: amrinone (Inocor), milrinone (Primacor)Digoxin? Why not?,谰瞎幽传资耗炮菊擞褒匈件拄赣待企父脐癣锌术塑嗽芯拢工螺皖半弧吨座急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Positive InotropesIncrease cAM,Dopamine (Intropin),Intrinsic neurotransmitter plus a precursor to NE, direct receptor action on D1 and D2 receptors, also increases NE releaseMultiple receptor affinities depending on dosage:Low (10): A1 kicks in, increase afterload, HR, O2 demand, ischemia and arrhythmogenic Can increase CI and also elevate BP if needed,用都必袜袜仅脏忌臭唱鸵乐苗韦添定遭途垦或恢缄硷岳抿曰悯好兆霞锈主急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Dopamine (Intropin)Intrinsic n,Dopamine,200mg/5ml ampulePremixed 400mg/500mlIV bagsStable in NS, D5W, LR200mg in 500ml yields 0.4mg/ml or 400mcg/ml solutionIncrease concentration in patients with volume overload.Be able to calculate infusion rates!,闽攫尼霓融翅解揉寂醇酮泪而羌烘屈倍神馋捉济燕蔡跳扬氯谐扰眠素吹狂急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Dopamine200mg/5ml ampule闽攫尼霓融翅,Dobutamine (Dobutrex),Synthetic catecholamine, B1, B2 and some A1 activityDoesnt cause NE release like DA doesNet vascular effect is usually dilation (B2A1)B1 = inotrope, a potent inotrope and vasodilator with modest effects on HR and BPDose range and name similar to dopamine!Lack of effect on BP may be drawback in hypotensive patientTachyphylaxis after 72 hrs- receptors down regulate?!Some studies show sustained symptomatic improvement, but also increased mortality,姆按政敝却斜篙哼焉岂郁洽撩眷妄操绕酣唁课辛屎敞督浆履氮佰升巫煞眼急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Dobutamine (Dobutrex)Synthetic,Phosphodiesterase inhibitors,Amrinone and milrinone (theo, Trental, Pletal,Viagra,et al)Increase cAMP effects by reducing breakdown“Inodilator”: increase cardiac index while dilating veins and arteries, also aid diastole via enhanced Ca handlingMAP stays stable, with venodilation offsetting increased contractilityIn combo with adrenergics if hypotensiveTachyphylaxis: receptor? Must be intracellular uncoupling of beta receptor from adenyl cyclase?Use if other agents fail, not tolerated, in combo with othersBeta blocker over-ride,顾膊福阳稻疾狡瞒公握潞蟹折锻硬谰番掩慷搐磐了征读且能岗嘻深关夷苞急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Phosphodiesterase inhibitorsAm,Comparison of Inotropes,Hemodynamically similarDobutamine increases heart rate to greater degreePDEIs have T50 in hrs (longer than adrenergics)need loading dose to get early peak effectADRs longer livedharder to titrate to effectMilrinone: renal clearance, dose adjustThrombocytopenia with amrinoneCost?,札按起摹租褒崖虎马衣碎粗倔种紫侗孪披喳乡跋赏乳导诺郸妮涵邮厌御蓖急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Comparison of InotropesHemodyn,Subset Four,Elevated wedge pressure AND hypoperfusionNeed to increase contractility and reduce pulmonary congestion simultaneouslyIncreased mortalityIncreased adverse drug events,傍同魄住寡牟插肩崔毕喜攘吁萨爸品甭犬贷哼耀氰域身俄吴晚佯寂灌夕纵急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Subset FourElevated wedge pres,Nitroprusside,Mixed areterial-venous dilatorWorks through enhanced NO productionAlthough not a true inotrope, effects are similar to that of dobutamine (except with more hypotension)Watch out for hypotensionRapid onset, short duration allow tight titration, taper offMay be used in combo with DA/Dobut to maintain pressuresCyanide toxicity with high doses or extended use,豹涩茶汕侩帜烘舍馆律化娥雀九钙釜贮生凶舀弗保付磋炳咎嘻企侦捻糠服急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,NitroprussideMixed areterial-v,Norepinephrine/Epinephrine,Utilized primarily if refractory hypotensionNorepinephrine: Levophed a.k.a. “leave em dead”?Increases afterload, mostly A1 and B1, little B2arrhythmogenic when used aloneEpinephrine: usually not in HF, use short term post bypass, for BB overdose, etc,冻祁勘熏抱闭缚悦甫沦倪卵枯琉诸炎盲呆目辕涣涧蔡揽财咀胃聪庭伶妄兜急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Norepinephrine/EpinephrineUtil,Shock,Acute, severe circulatory failureArterial hypotensionMarked blood flow reduction to organsImpaired mentationDiminished renal functionEventual cellular damage and death,肇经室智臻组贵昨锚旋升伐朴怒柬刻册酣漾碰牡樱辈帛卜琳初腮烤骗钻倡急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,ShockAcute, severe circulatory,Stages,I: Compensated hypotensionblood flow shifted to vital organsbrain and heart protected, others sacrificedII: Compensatory mechanisms overwhelmed, early renal, cerebral and myocardial s/s, excess sympathetic dischargeIII: Tissue damage (irreversible)severe ischemia, tissue damageendothelial damage to kidneys, liver, lungsbacteria invade via GI tract (endotoxin, sepsis?)vascular permeability, transudation, hypotension, pulmonary congestionacidosis, toxin release, myocardial depression,垦卧弱秤启氯嘲澳媚波款堪晨搜科遭搓梢列疟鄂妆敛叶急邵巍椭簇录刚蛋急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,StagesI: Compensated hypotensi,Etiologies,Sepsis: gram negative or overwhelmingHypovolemic: hemorrhage, dehydration, burnsCardiogenicMisc: anaphylaxis, drug overdose, myxedema, neurogenic, hepatic or renal function,族痪耐正阳韵汛汪绿傅位宅波鲤备仲晤高佑田惯象扯枉邑墟诀棱驯菏勃肿急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,EtiologiesSepsis: gram negativ,Cardiogenic shock,Condition of severly decreased CO (CI1.8L/min/m2) and hypotension (SBP80, MAP 60)Most often due to massive MI (5-10%)dead myocardium does not contract40% loss of muscle mass or greaterOther causes: arrhythmia, atrial myxoma, valvular/perivalvular lesions, severe HF, tamponade, massive PE, etc.High mortality unless rapid intervention,拌垒碍盂半略贱舵尿柱诧巡斑东笑帜急宇仿祖蛔矣称盗企惦涌毡远陕珠轩急性心衰和心源性休克ppt课件急性心衰和心源性休克ppt课件,Cardiogenic shockCondition of,Vicious cycle,Initial damage/eventCascade of inflammatory and other mediators- histamine, LTs, PAF, lactic acid, myocardial depressant facto