Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden...
Transcript of Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden...
![Page 1: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/1.jpg)
DeterminantsofNeonatalCardiacOutput
FjayFrickerMDNeonatologybasiccorecurriculum
![Page 2: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/2.jpg)
DeterminantsofcardiacoutputintheNeonate
DifferencesbetweenFetalandadultMyocardium
Organizationandthenumberofmyofbrilsundergochangesduringdevelopment.§ Orientationofmyofibrils§ Non-contractileelements
![Page 3: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/3.jpg)
DeterminantsofNeonatalCardiacOutput
FetalvsAdultMyocardium• ActiveTensionlowerthanadultatsamefiberlength(SystolicFunction)
• RestingtensiongreaterinFetusthanadult(Diastolicfunction)
• Sarcomeral lengthnotdifferent• Cannotbeexplainedbygreaterproportionofnoncontractileelements
• ?DifferentsensitivityoffetalcontractileproteinstocytosolicCalcium
![Page 4: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/4.jpg)
![Page 5: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/5.jpg)
DeterminantofCardiacOutputFetusVsadultAfterload
![Page 6: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/6.jpg)
StarlingCurveConceptofDescendingLimb
![Page 7: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/7.jpg)
DeterminantsofCardiacOutputTheSarcomere
![Page 8: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/8.jpg)
DeterminantsofCardiacOutputTheSarcomere
![Page 9: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/9.jpg)
DeterminantsofFetalCardiacoutput
MajorfactorsdeterminingCardiacOutput
• HeartRate• Preload• Afterload• Contractility
![Page 10: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/10.jpg)
HeartRateandStrokeVolumeHeartRateNeonateCardiacoutputmoredependentonHeartRate80-180bpm
![Page 11: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/11.jpg)
PressureVolumeLoopTheModel
![Page 12: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/12.jpg)
PressureVolumeLoopInterpretation
![Page 13: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/13.jpg)
PressureVolumeloop
![Page 14: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/14.jpg)
DeterminantsofCardiacOutputIncreaseinAfterLoad
![Page 15: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/15.jpg)
![Page 16: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/16.jpg)
DeterminantsofNeonatalcardiacOutput
Anrep EffectSuddenincreaseinafterloadontheheartcausesanincreaseinventricularinotropy.ThisPhenomenonisobservedindenervated hearts,isolatedmuscleandinintacthearts.Significanceisthattheincreasedinotropycompendates fortheincreasedendd-systolicvolumeanddecreasedstrokevolumecasusedbyincreaseinafterload.
![Page 17: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/17.jpg)
HeartFailureDefinition
• “..Heartfailureisaclinicalsyndromeinwhichheartdiseasereducescardiacoutput,increasesvenus pressures,andisaccompaniedbymolecularabnormalitiesthatcauseprogressivedeteriorationofthefailingheartandprematuremyocardialcelldeath”ARNOLDKATTZ
• Or• “TheHeartisunabletomeetthemetabolicdemandsofthe
body”
![Page 18: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/18.jpg)
HeartFailureCompensatoryChanges
![Page 19: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/19.jpg)
HeartFailure
EffectiveArterialBloodVolume
RenalVasoconstrictionReninAngiotensionAxis
NaandH2ORetension Reninrelease
Angiotension II
![Page 20: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/20.jpg)
HeartFailureConceptofforwardorbackwardfailure
Increasedintravascularvolume
IncreaseintheEnd-DiastolicPressureLVandRV
IncreaseinSystemicandPulmonaryVenousPressure
Hepatomegaly,Pulmonaryedemaandedema
![Page 21: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/21.jpg)
HeartFailure
RegionalCirculationSympatheticNervousAngiotensionIIsystem
Vasoconstriction
NAandH2OcontentofBloodvessels
![Page 22: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/22.jpg)
HeartFailureConcept
“BackwardorForwardFailure”
LiverCongestion/PulmonaryedemaRenalPerfusion
NaandH2O
IntravascularVolume RVEDPLVEDP LiverenlargementPulmonaryedema
![Page 23: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/23.jpg)
InotropesinNeonates
![Page 24: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/24.jpg)
Inotropes• Chosenaccordingtophysiologyandtitratedtoagoalto
beachieved• Combinationofdrugsismoreoftenusedtopreventside
effects• OtherfactorsaffectingCO:
– Acid-baseandelectrolytebalance(ex:acidosis,hypoCa)– Cardiopulmonaryinteractions(ex:ventilation)– Hypoxemia(ex:HIE,PH)– Presenceofintraorextracardiacshunts(ex:ASD,PDA)– Neuro-humoralresponse(ex:adrenal,thyroid,glucose)– Oxygencarryingcapacity(CaO2),OxygenConsumption(VO2=
metabolicdemands)– DysrhythmiasandlostofAVsynchrony– Patophysiology(Biventricularvs.SV)
Nicholz,HeartDiseaseinInfantsandChildren
![Page 25: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/25.jpg)
Ruoss,McPhersonandDiNardo,Neoreviews,2015
![Page 26: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/26.jpg)
Dopamine• Endogenouscatecholamineprecursorofnorepinephrineandepinephrine
• Receptors:alpha,beta,dopamine• Dosedependent:
– 0.5-2mcg/kg/min:dopaminergic recept (nobenefit)– 2-10mcg/kg/min:Beta1recept (éCOandSBP)– >10mcg/kg/min:alpharecept (vasoconstr,éSBPandDBP)
• UndesiredCVeffects:– oxygenconsumptionofmyocardium– automaticity(arrhythmias),tachycardia– 1pediatricstudy:associatedwithincreasedmortality- Venturaetal,PCCM2015
• Non-CVeffects:– Prolactin,thyrotropinandgrowth-hormonesecretionsuppression– Extravazation
Osborn, Evans,Kluckow,Neoreviews2004Ruoss,McPherson andDiNardo,Neoreviews,2015
![Page 27: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/27.jpg)
Dobutamine• Syntheticcatecholamine:doesnotreleaseNE• Receptors:beta1myocardium(é contractility)andB2peripheral(vasodil)
• UsedinmanyHIEstudies(êcontractility-LCOS)• Doses:
– >10mcg/kg/min:éCOandHR -Devictoretal.,ArchFrPed,1988
– 5-7.5mcg/kg/min:éCObutnotHRandBP -Martinezetal.,Pediatrics,1992
• Undesiredeffect:– Arrhythmia– Vasodilation Osborn, Evans,Kluckow,Neoreviews2004
Ruoss,McPherson andDiNardo,Neoreviews,2015
![Page 28: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/28.jpg)
Epinephrine• Endogenouscatecholamine• Receptors:alpha,beta• Predictabledose-dependentresponse(notinpreterms)
– 0.01- 0.1mcg/kg/min:betareceptors(b1>b2)– >0.1mcg/kg/min:alphareceptors(alpha1)
• NICU:oftenusedforrefractoryhypotension• UndesiredCVeffects:
– oxygenconsumption ofmyocardium– automaticity(arrhythmias)– Down-regulatesreceptors
• Non-CVeffects:• HypoK:B2mediatedKinflux tomusclecells• Hyperglycemia: glycolisisandsupressesinsulin release• Intestinalhypoperfusion -Cheung etal.,1997• Extravazationinjury
Osborn, Evans,Kluckow,Neoreviews2004Ruoss,McPherson andDiNardo,Neoreviews,2015
![Page 29: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/29.jpg)
Norepinephrine• Endogenouscatecholamine• Receptor:alpha1and2(ééSVR-potentvasoconstrictor).LessextentB1and2.
• Doses:0.01-0.4mcg/kg/min• Undesiredeffects:
– afterloadtotheheart(workload)– Poorend-organperfusion(kidneysandgut)- tissueischemia– Extravazationinjury
• Usualindications:lowSVR(vasodilated-septicshock),hypertrophiccardiomyopathieswithhypotension
Osborn, Evans,Kluckow,Neoreviews2004Ruoss,McPherson andDiNardo,Neoreviews,2015
![Page 30: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/30.jpg)
Dopamineordobutamine?
-Dopamine: more effective in the short term treatment of hypotension in preterm infant-No evidence of adverse neurological sequelae (severe P/IVH and/or PVL)
Subhedar andShaw,Cochrane2003
“intheabsenceofdataconfirminglongtermbenefit…dopaminecomparedtodobutamine,nofirmrecommendationscanbemaderegardingthechoiceofdrugtotreathypotension.”
![Page 31: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/31.jpg)
Milrinone• Bipyridinegroup:selectivephosphodiesterase-3inhibitor.• IncreasescytosoliccAMPw/oreceptormechanism:positive
inotropicandlowersSVR(Inodilator)asperpetuates influxofCalcium=éCO
• Pulmonaryhypertension:weakvasodilator• DrugofchoicetobalanceQP:QSandpreventLCOSaftercardiac
surgery• Doses:0.25-1mcg/kg/min• UndesiredCVeffects:
– Hypotension– Tachycardia/arrhythmia
• Non-CVeffects:– Thrombocytopenia– Carefuladministrationwhenrenaldysfunction
Osborn, Evans,Kluckow,Neoreviews2004Ruoss,McPherson andDiNardo,Neoreviews,2015
![Page 32: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/32.jpg)
DopamineorEpinephrine?
– Dcauses10%decreaseLVoutput secondarytodropinLVstrokevolume;EincreasesLVoutput by10%duetoincreaseinLVS
– Conclusion:“Epinephrinehasbettereffectoncontractility”
•20pts, >1750g•D:5,10,15,20mcg/kg/min•E:0.125,0.250,0.375,0.5mcg/kg/min
•60pts,<1501g•D:2.5,5,7.5,10mcg/kg/min•E:0.125,0.250,0.375,0.5mcg/kg/min
– Nodifferencesfoundratetreatmentfailure– Conclusion:“Low/mod-dose Eisaseffectiveaslow/moddoseD fortreatment
hypotension inlowbirthweightinfants,althoughisassociatedwithmoretransitoryadverseeffects”
Pediatrics,2006
MORESTUDIESNEEDED!
![Page 33: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/33.jpg)
Steroids
• Mechanismofaction:– Decreasesthebreakdownofcatecholamines– Increasescalciumlevelsinmyocardialcells– Upregulates adrenergicreceptors– Innapropriate cortisol secretionduringsickness(relativeadrenal
insufficiency)• Dose:50mg/m2/day• Adverseeffects:
– Hyperglycemia– Gastricirritation– Fluidretention– Long-term:osteopenia,immunossupression,decreasedsomatic
growth,asseptic acetabular necrosis
Ruoss,McPherson andDiNardo,Neoreviews,2015
![Page 34: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/34.jpg)
Frank-StarlingCurveThehearthasanintrinsiccapabilitytoincreaseitsforceofcontractionandthereforestrokevolume(SV)inresponsetoan
increaseinvenous return. ThisiscalledtheFrank-Starlinglaw(Fig2).Theraiseofvenous returnincreasestheventricularfilling(end-diastolicvolume)andthereforepreload,whichextendsthemyocyte sarcomerelength,causinganincreasein
forcegeneration.Theunderlyingmechanismisfound in thelength-tension andforce-velocityrelationships forcardiacmyocytes.Briefly,increaseofsarcomerelengthenhancestroponin Ccalciumsensitivity, whichupregualtes therateofmyosin-actinattachmentanddetachment,andtheamountoftension developedbythemusclefiber.
Isthereadescendinglimbofthestarlingcurve?
![Page 35: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/35.jpg)
HeartFailureContractility
![Page 36: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/36.jpg)
Isoproterenol
• Syntheticcatecholaminestructurallyrelatedtoadrenaline
• Receptor:almostexclusivelyBeta(éHR)• Doses:0.01-0.1mcg/kg/min• Undesiredeffects:
– oxygenconsumptionofmyocardium– automaticity(arrhythmias)– Extravazationinjury
• Usualindications:congenitalheartblock,PPHN,posthearttransplant(denervatedheart)
Osborn, Evans,Kluckow,Neoreviews2004
![Page 37: Determinants of Neonatal Cardiac Output...Determinants of Neonatal cardiac Output AnrepEffect Sudden increase in afterload on the heart causes an increase in ventricular inotropy.](https://reader033.fdocuments.net/reader033/viewer/2022052720/5f08a8fd7e708231d4231a69/html5/thumbnails/37.jpg)
Vasopressin• NeuropeptideactingonV1andV2receptorsonsmooth
musclecellsandNOselectivevasodilationofcerebralandpulmonarycirculations
• Possiblesynergisticactiontocathecolamines• Peripheralvasoconstr(exceptCNS,coronary,gut,lungs)• Uses:
– Septicshock– Post-CPB
• Doses:0.0001-0.002Units/kg/min• Adverseeffects:vasoconstriction,tissuenecrosisand
hyponatremia
Maffei,PediatricCriticalCareStudyGuide,2012Ruoss,McPherson andDiNardo,Neoreviews,2015