DeterminantsofNeonatalCardiacOutput

FjayFrickerMDNeonatologybasiccorecurriculum

DeterminantsofcardiacoutputintheNeonate

DifferencesbetweenFetalandadultMyocardium

Organizationandthenumberofmyofbrilsundergochangesduringdevelopment.§ Orientationofmyofibrils§ Non-contractileelements

DeterminantsofNeonatalCardiacOutput

FetalvsAdultMyocardium• ActiveTensionlowerthanadultatsamefiberlength(SystolicFunction)

• RestingtensiongreaterinFetusthanadult(Diastolicfunction)

• Sarcomeral lengthnotdifferent• Cannotbeexplainedbygreaterproportionofnoncontractileelements

• ?DifferentsensitivityoffetalcontractileproteinstocytosolicCalcium

DeterminantofCardiacOutputFetusVsadultAfterload

StarlingCurveConceptofDescendingLimb

DeterminantsofCardiacOutputTheSarcomere

DeterminantsofCardiacOutputTheSarcomere

DeterminantsofFetalCardiacoutput

MajorfactorsdeterminingCardiacOutput

• HeartRate• Preload• Afterload• Contractility

HeartRateandStrokeVolumeHeartRateNeonateCardiacoutputmoredependentonHeartRate80-180bpm

PressureVolumeLoopTheModel

PressureVolumeLoopInterpretation

PressureVolumeloop

DeterminantsofCardiacOutputIncreaseinAfterLoad

DeterminantsofNeonatalcardiacOutput

Anrep EffectSuddenincreaseinafterloadontheheartcausesanincreaseinventricularinotropy.ThisPhenomenonisobservedindenervated hearts,isolatedmuscleandinintacthearts.Significanceisthattheincreasedinotropycompendates fortheincreasedendd-systolicvolumeanddecreasedstrokevolumecasusedbyincreaseinafterload.

HeartFailureDefinition

• “..Heartfailureisaclinicalsyndromeinwhichheartdiseasereducescardiacoutput,increasesvenus pressures,andisaccompaniedbymolecularabnormalitiesthatcauseprogressivedeteriorationofthefailingheartandprematuremyocardialcelldeath”ARNOLDKATTZ

• Or• “TheHeartisunabletomeetthemetabolicdemandsofthe

body”

HeartFailureCompensatoryChanges

HeartFailure

EffectiveArterialBloodVolume

RenalVasoconstrictionReninAngiotensionAxis

NaandH2ORetension Reninrelease

Angiotension II

HeartFailureConceptofforwardorbackwardfailure

Increasedintravascularvolume

IncreaseintheEnd-DiastolicPressureLVandRV

IncreaseinSystemicandPulmonaryVenousPressure

Hepatomegaly,Pulmonaryedemaandedema

HeartFailure

RegionalCirculationSympatheticNervousAngiotensionIIsystem

Vasoconstriction

NAandH2OcontentofBloodvessels

HeartFailureConcept

“BackwardorForwardFailure”

LiverCongestion/PulmonaryedemaRenalPerfusion

NaandH2O

IntravascularVolume RVEDPLVEDP LiverenlargementPulmonaryedema

InotropesinNeonates

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

Ruoss,McPhersonandDiNardo,Neoreviews,2015

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

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

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

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

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.”

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

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!

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

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?

HeartFailureContractility

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

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