Download Determinants of Neonatal Cardiac Output

DeterminantsofNeonatal
CardiacOutput
FjayFrickerMD
Neonatologybasiccorecurriculum
Determinantsofcardiacoutputinthe
Neonate
DifferencesbetweenFetalandadult
Myocardium
Organizationandthenumberofmyofbrils
undergochangesduringdevelopment.
§ Orientationofmyofibrils
§ Non-contractileelements
DeterminantsofNeonatalCardiac
Output
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FetalvsAdultMyocardium
ActiveTensionlowerthanadultatsamefiber
length(SystolicFunction)
RestingtensiongreaterinFetusthan
adult(Diastolicfunction)
Sarcomeral lengthnotdifferent
Cannotbeexplainedbygreaterproportionofnon
contractileelements
?Differentsensitivityoffetalcontractileproteins
tocytosolicCalcium
DeterminantofCardiacOutput
FetusVsadult
Afterload
StarlingCurveConceptofDescending
Limb
DeterminantsofCardiacOutput
TheSarcomere
DeterminantsofCardiacOutput
TheSarcomere
DeterminantsofFetalCardiacoutput
MajorfactorsdeterminingCardiacOutput
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HeartRate
Preload
Afterload
Contractility
HeartRateandStrokeVolume
HeartRateNeonate
Cardiacoutput more
dependent on Heart
Rate80-180bpm
PressureVolumeLoop
TheModel
PressureVolumeLoop
Interpretation
PressureVolumeloop
DeterminantsofCardiacOutput
IncreaseinAfterLoad
DeterminantsofNeonatalcardiac
Output
Anrep Effect
Suddenincreaseinafterloadontheheart
causesanincreaseinventricularinotropy.This
Phenomenonisobservedindenervated hearts
,isolatedmuscleandinintacthearts.
Significanceisthattheincreasedinotropy
compendates fortheincreasedendd-systolic
volumeanddecreasedstrokevolumecasused
byincreaseinafterload.
HeartFailure
Definition
• “..Heartfailureisaclinicalsyndromeinwhichheartdisease
reducescardiacoutput,increasesvenus pressures,andis
accompaniedbymolecularabnormalitiesthatcause
progressivedeteriorationofthefailingheartandpremature
myocardialcelldeath”ARNOLDKATTZ
• Or
• “TheHeartisunabletomeetthemetabolicdemandsofthe
body”
HeartFailure
CompensatoryChanges
HeartFailure
EffectiveArterialBloodVolume
RenalVasoconstrictionReninAngiotension
Axis
NaandH2ORetension Reninrelease
Angiotension II
HeartFailure
Conceptofforwardorbackwardfailure
Increasedintravascularvolume
IncreaseintheEnd-DiastolicPressureLVandRV
IncreaseinSystemicandPulmonaryVenousPressure
Hepatomegaly,Pulmonaryedemaandedema
HeartFailure
RegionalCirculation
SympatheticNervousAngiotensionII
system
Vasoconstriction
NAandH2OcontentofBloodvessels
HeartFailure
Concept
“BackwardorForwardFailure”
LiverCongestion/Pulmonaryedema
RenalPerfusion
NaandH2O
IntravascularVolume
RVEDPLVEDP
Liverenlargement
Pulmonaryedema
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)
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Nicholz,HeartDiseaseinInfantsandChildren
Ruoss,McPherson andDiNardo,Neoreviews,2015
Dopamine
• Endogenouscatecholamineprecursorofnorepinephrine
andepinephrine
• 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,thyrotropin andgrowth-hormonesecretionsuppression
– Extravazation
Osborn, Evans,Kluckow, Neoreviews2004
Ruoss, McPherson andDiNardo,Neoreviews,2015
Dobutamine
• Syntheticcatecholamine:doesnotreleaseNE
• Receptors:beta1myocardium(é contractility)
andB2peripheral(vasodil)
• UsedinmanyHIEstudies(êcontractility-LCOS)
• Doses:
– >10mcg/kg/min: éCOandHR
-Devictoret
al.,ArchFrPed,1988
– 5-7.5mcg/kg/min:éCObutnotHRandBP
1992
-Martinezetal.,Pediatrics,
• 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:
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HypoK: B2mediatedKinflux tomusclecells
Hyperglycemia:­ glycolisisandsupressesinsulin release
Intestinalhypoperfusion
Extravazationinjury
-Cheung etal.,1997
Osborn, Evans,Kluckow, Neoreviews2004
Ruoss, McPherson andDiNardo,Neoreviews,2015
Norepinephrine
• Endogenouscatecholamine
• Receptor:alpha1and2(ééSVR-potent
vasoconstrictor).LessextentB1and2.
• Doses:0.01-0.4mcg/kg/min
• Undesiredeffects:
– ­ afterloadtotheheart(workload)
– Poorend-organperfusion(kidneysandgut)- tissueischemia
– Extravazationinjury
• Usualindications:lowSVR(vasodilated-septic
shock),hypertrophiccardiomyopathieswith
hypotension
Osborn, Evans,Kluckow, Neoreviews2004
Ruoss, 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)
“intheabsenceofdataconfirminglongtermbenefit…dopamine
comparedtodobutamine,nofirmrecommendationscanbemaderegarding
thechoiceofdrugtotreathypotension.”
Subhedar andShaw,Cochrane2003
Milrinone
• Bipyridinegroup:selectivephosphodiesterase-3inhibitor.
• IncreasescytosoliccAMPw/oreceptormechanism:positive
inotropicandlowersSVR(Inodilator)asperpetuatesinfluxof
Calcium=éCO
• Pulmonaryhypertension:weakvasodilator
• DrugofchoicetobalanceQP:QSandpreventLCOSaftercardiac
surgery
• Doses:0.25-1mcg/kg/min
• UndesiredCVeffects:
– Hypotension
– Tachycardia/arrhythmia
• Non-CVeffects:
– Thrombocytopenia
– Carefuladministrationwhenrenaldysfunction
Osborn, Evans,Kluckow, Neoreviews2004
Ruoss, McPherson andDiNardo,Neoreviews,2015
DopamineorEpinephrine?
•20pts, >1750g
•D:5,10,15,20mcg/kg/min
•E:0.125,0.250,0.375,
0.5mcg/kg/min
– Dcauses10%decreaseLVoutput secondarytodropinLVstrokevolume;EincreasesLV
output by10%duetoincreaseinLVS
– Conclusion:“Epinephrinehasbettereffectoncontractility”
•60pts,<1501g
•D:2.5,5,7.5,10mcg/kg/min
•E:0.125,0.250,0.375,
0.5mcg/kg/min
Pediatrics,2006
– Nodifferencesfoundratetreatmentfailure
– Conclusion:“Low/mod-dose Eisaseffectiveaslow/moddoseD fortreatment
hypotension inlowbirthweightinfants,althoughisassociatedwithmoretransitory
adverseeffects”
MORESTUDIESNEEDED!
Steroids
• Mechanismofaction:
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Decreasesthebreakdownofcatecholamines
Increasescalciumlevelsinmyocardialcells
Upregulates adrenergicreceptors
Innapropriate cortisol secretionduringsickness(relativeadrenal
insufficiency)
• Dose:50mg/m2/day
• Adverseeffects:
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Hyperglycemia
Gastricirritation
Fluidretention
Long-term:osteopenia,immunossupression,decreasedsomatic
growth,asseptic acetabular necrosis
Ruoss, McPherson andDiNardo,Neoreviews,2015
Frank-StarlingCurve
Thehearthasanintrinsiccapabilitytoincreaseitsforceofcontractionandthereforestrokevolume(SV)inresponsetoan
increaseinvenous return. ThisiscalledtheFrank-Starlinglaw(Fig2).Theraiseofvenous returnincreasestheventricular
filling(end-diastolicvolume)andthereforepreload,whichextendsthemyocyte sarcomerelength,causinganincreasein
forcegeneration.Theunderlyingmechanismisfound in thelength-tension andforce-velocityrelationships for
cardiacmyocytes.Briefly,increaseofsarcomerelengthenhancestroponin Ccalciumsensitivity, which
upregualtes therateofmyosin-actinattachmentanddetachment,andtheamountoftension developedbythemusclefiber.
Isthereadescendinglimb
ofthestarlingcurve?
Contractility
HeartFailure
Isoproterenol
• Syntheticcatecholaminestructurallyrelatedto
adrenaline
• 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
musclecellsandNOselectivevasodilationofcerebraland
pulmonarycirculations
• Possiblesynergisticactiontocathecolamines
• Peripheralvasoconstr(exceptCNS,coronary,gut,lungs)
• Uses:
– Septicshock
– Post-CPB
• Doses:0.0001-0.002Units/kg/min
• Adverseeffects:vasoconstriction,tissuenecrosisand
hyponatremia
Maffei,PediatricCriticalCareStudy Guide,2012
Ruoss, McPherson andDiNardo,Neoreviews,2015