PulmonaryHypertensionForTheAnaesthetist

Dr.RuthNewton2017

WiththankstoDr.V.Wilson,ProfI.Sabroe,Prof.D.Kiely,DrR.Condliffe,Dr A.Charalampopoulos

PulmonaryHypertensionForTheAnaesthetist

• Definitions• Pathophysiology• Treatment• Pre-operativeassessment• Perioperativecare• CaseStudies

PulmonaryHypertensionForTheAnaesthetist

“Pulmonaryhypertension(PH)isahaemodynamic andpathophysiologicalconditiondefinedasanincreaseinmean

pulmonaryarterialpressures≥25mmHgatrestasassessedbyrightheartcatheterisation”

Classification(5th WorldSymposiumNice,France2013)

1. PulmonaryArteryHypertension(PAH)2. PulmonaryHypertension(PH)duetoleft

heartdisease3. PHduetolungdiseasesand/orhypoxaemia4. ChronicThromboembolicPulmonary

Hypertension(CTEPH)5. Pulmonaryhypertensionwithunclear

multifactorialmechanisms

1.1IdiopathicPAH1.2Hereditable(i/BMPR2,ii/ALK1,endoglin (withor

withouthereditaryhaemorrhagic telangectasia iii/unknown)

1.3Drugandtoxininduced1.4Associatedwith

-Connectivetissuediseases-HIVinfection-Portalhypertension-Congential heartdisease(i/Eisenmengers,ii/prevalentsystemictopulmonaryshuntsiii/smallcardiacdefectsivPAH afterdefectcorrection-Schistosomiasis-Chronichaemolytic anaemia

1’ Pulmonaryveno-occlusivediseaseand/orpulmonary capillaryhaemangiomatosis1’’ Persistant pulmonaryhypertensionofthenewborn

1. PAH

1. PHduetoleftheartdisease

1. PHduetolungdisease/hypoxaemia

1. CTEPH

1. PH2. unclear/mult

ifactoria

1.PAH

• PAH“pulmonaryveno-occlusivediseaseorpulmonarycapillaryhemangiomatosis”– Medialhypertrophy– Muscularization ofarterioles– Cellularproliferationofintimalayer– Concentriclaminarintimalfibrosis– Plexiform lesions– Fibrinoid necrosis

Group1:pulmonaryarterialhypertension

“Pulmonaryarterialhypertension(PAHGroup1)isaclinicalconditioncharacterised bythe

presenceofpre-capillaryPH(PAPm≥25mmHgandPAWP≤15mmHg”

ClassificationGroup2PAH

2.1Leftventricularsystolicdysfunction2.2Leftventriculardiastolicdysfunction2.3Valvular disease2.4Congenital/aquired leftheartinflow/outflowtractobstructionandcardiomyopathies

1. PAH

1. PHduetoleftheartdisease

1. PHduetolungdisease/hypoxaemia

1. CTEPH

1. PHunclear/multifactorial

2.PHduetoL.heartdisease

–medialhypertrophy

–muscularization ofarteriolesandveins

– non-obstructiveintimalfibrosis

–moderateintimafibrosisveins

ClassificationGroup3PH

3.1COPD3.2Interstitiallungdisease3.3Otherpulmonarydiseaseswithmixedrestrictiveandobstructivepattern3.4Sleepdisorderedbreathing3.5Alveolarhypoventilationidisorders3.6Chronicexposuretohighaltitude3.7Developemental abnormalities

1. PAH

1. PHduetoleftheartdisease

1. PHduetolungdisease/hypoxaemia

1. CTEPH

1. PHunclear/multifactorial

3.PHduetolungdisease/hypoxaemia

– Largearteriesmostlynormal

– Medialhypertrophy

– Muscularisation ofarterioles

– Similarchangestolesserextentinsmallpulmonaryveins

ClassificationGroup41.PAH2.PHduetoleftheartdisease3.PHduetolungdisease/hypoxaemia

1.CTEPH- mildmedialhypertrophy- eccentricintimalfibrosis- recanalisation oflumen- recentthrombirare

1.PHunclear/multifactorial

ClassificationGroup5PAH5.1Haematologic disorders:chronichaemolytic anaemia,myeloproliferative disorders,splenectomy5.2Systemicdisorders:sarcoidosis,pulmonaryhistocytosis,lymphangioleiomyomatosis5.3Metabolicdisorders:glycogenstoragedisease,gaucher disease,thyroiddisorders5.4Others:tumoral obstruction,fibrosing mediastinitis,chronicrenalfailure

1. PAH

1. PHduetoleftheartdisease

1. PHduetolungdisease/hypoxaemia

1. CTEPH

1. PHunclear/multifactorial

5.PHunclear/multifactorialpathology• Muscularisation ofarteriolesandveins(fibroticlungdiseasem tumours)• Non-obstructiveintimalfibrosis(fibroticlungdiseaseandtumours)• Vasculargranulomas(sarcoidosis,tuberculosis)• Enlargementofbronchialarteries(bronchiectasis

PulmonaryEndothelialInjury

GeneticPredisposition

Pulmonaryvasoconstriction

Endothelialre-modelling

SustainedPH

Hypoxia

↓Fibrinolysis

Coagulationdefects

↑ET-1,PGI2,TB

↓NO,Kchanneldefects

↑PDGF,VEGF,TGF-β

Physiology• LowPressureSystem- rightheartthinmusclePulmonaryvasoconstrictioninresponseto

- Hypoxia- Acidocis- Hypercarbia- Noradrenalin/Adrenalin/Serotonin/Histamine- Endothelin pathway

• Increasedpressureinpulmonaryvasculature- Largeinspiratoryvolume- Positivepressureventilation- PEEP

• Vasorelaxation- Nitricoxidepathway- Prostacyclinpathway

Physiology

• Rightheartfailure• Backwardfailure• Forwardfailure• Hypoxia– Righttoleftshunt– Relativelyfixedcardiacoutput:

extraction>delivery

– Ventilationperfusionmismatch– Pulmonaryvasoconstictionçè Hypoxia

Generic20th CenturyTherapy

• Generic20th century• Diuretics• Digoxin• Anticoagulation• Ca channelblockers• Prostacyclin• Atrialseptoplasty• Transplant• Pulmonaryendarterectomy

Targetedtherapy2017• Phosphodiesterase inhibiters– Sildenafilpo/iv[po:2005][iv:2009]andtadalafil [po 2009]

• Endothelin receptorantagonists– Macitentan(2013),bosentan po [2001],andambrisentan[2007],sitaxentan po [EU2007- nowwithdrawn]

• Prostanoid analogues– epoprostenol iv[iv:1995][iv:new formulation2008]– Iloprost neb/iv[neb:2004, iv]– Treprostinil sc/neb/iv[s/c2002][iv2004][inh:2009] (PO2013)(implantableiv–researchonly)

– Selexipag [po](researchonlycurrently)• Guanylate cyclase stimulator– riociguat (FDAapproval2013)

TsaiH,SungYKanddeJesusPerezV.Recentadvancesinthemanagementofpulmonaryarterialhypertension

[version1;referees:2approved]F1000Research2016,5(F1000FacultyRev):2755(doi:10.12688/f1000research.9739.1)

PerioperativeCare• Perioperativemortality7-18%• Perioperativemorbidity14-

42%- PHcrisis- Heartfailure

- Respiratoryfailure- Dysrhythmias- Sepsis- Renalinsufficiency- Myocardialinfarction- Pulmonaryembolism

Pilkingtonetal.Anaesthesia.2015;70,56-70

Perioperativeconsiderations• Pre-op;Istheconditionoptimallytreated

- TypeI,byPHphysiciansusingpulmonaryvasodilators- TypeII,underlyingcardiacconditionoptimallymanagedby

cardiologists- TypeIII,underlyinglungdiseaseoptimallymanagedby

respiratoryphysicians- TypeIV,bridginganticoagulationplanandpatientson

pulmonaryvasodilatorsmanagedbyPHphysisicans- TypeV,managedbyPHphysicians,recentimagingasindicated

• Isthesurgerynecessary• Havetherisksbeendiscussed–

surgeons/physicians/anaesthetists/criticalcare/patient• Doesthepatientneedcriticalcarepre-operatively/post-operatively

Glasgow:GoldenJubileeNationalHospital

Newcastle:FreemanHospital

Sheffield:RoyalHallamshireHospital

Dublin:MisercordiaeUniversityHospital

Cambridge:PapworthHospital

London:RoyalFree,GreatOrmand Street,Hammersmith,RoyalBrompton

www.pulmonaryhypertensioncerters.co.uk

Pre-operativeAssessment:Symptoms

• Unexplainedbreathlessnessonexcertion• Chestpainonexcertion• Syncopeonexcertion….indicatorofinadequatecardiacoutputandseveredisease• Breathlessnessatrest……?pulmonaryoedema,?PHsecondarytoleftheartdisease• Chestpain(similartoangina)• Syncopeatrest……..besuspiciousofarrythmias• FamilyhistoryofunexplainedSOB,exertionalsyncope,suddendeath…alerttopossibilityofPH

Pre-operativeassessment:signs

• Minimalsignsinearlydisease• Severediseasewithdecompensatedrightheartfailure;– tachycardia– elevatedjvp,rightventricularheave– tricuspidregurg,– hepatamegaly andascites– ankleswelling

Pre-operativeassessment:investigations

• 6minShuttlewalk(withSP02),CPEX• ECG• CXR• Pulmonaryfunctiontests(typeIII)• Echocardiogram• RightheartcatheterisationwithvasodilatorchallengeandCV02measurment

• HRCT/VQ/CTPAasindicated• CardiacMRI• Bloods:routinehaematology andbiochemistry,coagulationmonitoring,BNPorNT-proBNP

ECG

CXR

IPAH:preandpostivprostanoid therapy

Echo

ERC/ERSguidelines2016

Other“PHsigns”from2ormorecatagoriesmustbepresenttoalterthelevelofechocardiographicprobabilityofPH

Rightheartcatheterisation andvasoreactivity

• PressuremeasurementsinthePA,PAwedge,RVandRA

• SVO2– samplesfromhighSVC,andPA+moreifshuntsuspected+ABGsample

• COusingthermodilution orfick• Pulmonaryvasoreactivity testing(CCB),NO10-20ppm,oriloprost (neb/iv).PositiveifdropinmeanPAP>10toreachmeanPAPof<40

CTPA

PA LVRARV

CardiacMRILeft VentricleLVEDV(LVEDVI) 69ml(44.6ml/m2)LVESV(LVESVI) 21.5ml(13.9ml/m2)SV (SVI) 47.5ml(30.7ml/m2)EF 69%HR 95CO (CI) 4.5L/min(2.9L/min/m2)RightVentricleRVEDV(RVEDVI) 96.7ml (63.6m/m2)RVESV(RVESVI) 42.7ml(27.6ml/m2)SV 56.0mlEF 57%

Pre-operativeassessment:investigations

• 6minShuttlewalk(withSP02),CPEX• ECG• CXR• Pulmonaryfunctiontests(typeIII)• Echocardiogram• RightheartcatheterisationwithvasodilatorchallengeandCV02measurment

• HRCT/VQ/CTPAasindicated• CardiacMRI• Bloods:routinehaematology andbiochemistry,coagulationmonitoring,BNPorNT-proBNP

Riskstratificationfornoncardiacsurgery

McLaughlinVV,McGoon MD.Circulation.2006Sep26;114(13):1417-31

Factor Lower risk Higherrisk

ClinicalRVfailure No Yes

Progression Gradual Rapid

WHOClass II,III IV

6minuteshuttle >400m <300m

BNP Minimallyelevated

Veryelevated: at diagnosis>150at f/u>180

Echo findings MinimalRVdisfunction

Pericardial effusion,significantRVdysfunction

Haemodynamics NormalRAP&CI

ElevatedRAP>10mmHgLowCI<2L/kg/m2

RiskofmortalityinPH

ERC/ERSguidelines2016

MDTAnaesthetist:Modeofanaesthesia,timingofsurgerySurgeon:considerationoftimingandsurgicaltechniqueRespiratoryPhysician&PHnursespecialistOtherspecialistphysiciansPharmacist:post-operativeIVPHdrugsHaematologist:anticoagulationCriticalCarePhysician:perioperativecriticalcareTheatremanager:seniorteamforhighriskcasePatientandfamily(Obstetricians/midwives/neonatologyteampluscommunicationwiththeirlocalhospital)

AnaesthesiaGAvs RA

↓ venousreturn ↓ cardiacoutput

↑PVRand/or↓ RVfunction

↑ alveolarpressurewithcompressionofpulmonaryvasculature

↑ hypoxicpulmonary

vasoconstriction

↑ pro-inflammatory

state

↑ sympatheticstimulationduring

airwayinstrumentationandtrachealintubation

Oxygenation

Sedation

SVR

Pneumoperitonium

Cardiacstability

Bloodloss

Analgesia

Vagalresponse

PEEP

IPPV

Laryngoscopy

Monitoring

ECGSpO2

Arterialline,SAO2,lactateCVP/PAintroducer,SVO2DopplerLithiumDilutionCardiacOutput(LiDCO)TTE/TOE(PAintroducer,swann ganz selectedcasesonly)

Kiely DGetal.In HeartDiseaseandpregnancyRCOGPress,2006;pp 211-29.

AnaesthesiaMaintainRVpreload,minimise afterload

AnaesthesiaOxygenAnxiolysis (TCIremifentanil)Avoidsympatheticstimulationsurgical/laryngoscopyAvoidhypoxiaAvoidacidosisAvoiddropping SVRAvoidarrythmiasFluidbalance- knifeedgeManageRVischaemia andfailureaggressively

AdvancedPHtherapyContinuepre-operativePHtherapyConsiderperi-operativeIViloprost/ IVsildenafilPlanforanticoagulationRESCUE Rescucitation:50mcgbolus iloprost.Isinvasivesupportappropriate?

SurgeryspecificOrthopedics *bewarecement*Laparoscopy*pneumoperitoneum*Obstetric*IncreasedplasmavolumeandQp**Peripartum instability**uterotonics*Thoracic*1lungventilation*

VentilationSV,facemaskandO2+/- volatileorTCIpropofol forminor surgeryVentilation;O2;lungprotectivestrategywithminimalpressures, increaseFiO2ratherthanexcessivePEEP

AnalgesiaRA,Neruoaxial (bewareê SVR)Opioidbutavoidrespiratorydepression

InotropesandpulmonaryvasodilatorsDrug PAP PCWP Qp SAP HR PVR

Noradrenalin ñ ñtoññ

- ññ - ñ

Phenylephrine ññ - ê ññ ê ñ

Adrenalin ñ - ñ ññ ñ ñ

Dobutamine ñ ê ññ ñ ñ ê

Vasopressin -/ñ ñ *∨CO ññ -/ê ñ

Milrinone ê ê ñ ê ñ ê

Epoprostenol ê - ñ ê ñ ê

Iloprost êê - ññ - - êê

NitricOxide êê ñ ññ - - êê

Case1

Frail80yroldmildPHduetoleftventriculardiastolicdysfunctionforcystectomyandileal conduits.

• On40mgfrusemide bd for“4limblymphodema”started30yearsago.ProlongedITUstayfollowingkneereplacementswithpneumonia.Poormobilityasnevermobilisedwellpostop.

• Echo - mildLVdiastolicdysfunction- dilatedrightventriclewithgoodfunction- severelydilatedatria- raisedsystPAP 34-40mmHg- moderateTR,mildMRandPR

Case2:Haematological andPAH/CTEPHforsplenectomy

• PAHinassociationwithlymphomaandVTE• Lymphoma,splenomegally,hilar lymphnodes,recurrentDVT• WHOII/III,Shuttle220mminimumSPO278%• Lungfunction;FEV170%,FVC74%normalFEV1/FVCratio,

TLCO35%andKCO61%• RightHeartCatheterisationmeanPApressure44mHgCI

4.3l/min/m2,PVR380dynaes.• Lefttorightshuntonauantitative Qscan• CardiacMR:goodLVandRVfunction.• Drugs:Erythromycin,Treatmentdosedalteparin,Frusemide,

Sildenafil25mgtds,Methadone.O2prn.• MDT,Intensivists,PHpysician,haematology,anaesthetist,

generalsurgeon

Case3

IdiopathicpulmonaryarteryhypertensionwithmoderatelysevereRVimpairmentandpregnant

• Lastclinicalreviewat29+5

• Shuttle430mwithSPO2minimum86,WHOIII• MRI25weeksLVEF59%,CI2.9L/min,RVEF57%,RVESVI

27.6ml• Dx,Sildenafil50mgtds,iloprostnebs5mcg6xdaily,LMWH,

Ferroussulphate,pregnancyvitamins.

Case3

Case3• MDTandexpertcareinPHcenter• Regularreviewandfunctionalassessmentthroughpregnancy

adjustPHtherapyasrequired.(Endothelin receptorantagonistsmustbestopped)

• Aimtodeliverataround35weeks• Admit2dayspre-operatively,startIViloprostandincreaseas

tolerated/required• AdmitITU1daypre-operatively,placelinesandestablish

baselinemonitoring,increaseiloprostasrequired• LithiumdilutionCOmonitoring• LowdoseremifentanilTCIforanxiolysis• AttachvasopressorivandinotropestoCVline• CSEwithlowdosespinal• 5usynt over1hour(myometrial carboprost,Blynch,

misoprostil inreserve)

Case4• FHx HereditaryPAHtelangectasia gene• SOBwalkingroomtoroomandcollapseinpregnancy

investigated,CTandEchoconsistentwithpulmonaryhypertension– referredtospecialistcenterat17wks.

• EchoImpairedRVestimatedsPAP of100mmHg• CTopacification noPE• CardiacMRIVerydilatedRV,RVhypertrophy+impaired

function,flattening,paradoxicalseptal motion,LVcompression

• Sildenafil,iloprost nebs• NoobviousfeaturesofHHT.Sympt ofrighthipthigh

numbness,urgentMRAimaging……multipleAVmalformations

Case5FracturedNOFinterminallyill75yearoldwithlungcancer(massobstructingleftmainandlowerlobebronchi),PE6monthsago.Mobilises withassistanceof2.

• V.lowdoseremi TCIforanalgesiaandanxiolysis• FasciaIliaca block• Lowdosespinal• Mildlyhypotensive…..givenmeteraminol• Hypotensiveandgrosslyhypoxic• Starteddobutamine• Uncemented hemiarthroplasty

ClosingRemarks

➢ Naturalhistoryvariableandsurvivalisimproving

➢ Highperi-operativemorbidityandmortality

➢ Advisedofhighriskassociatedwithsurgeryandpregnancy

➢ Multi-professionalapproachimprovessurvival

➢ Extendedperi-operativestayincriticalcareenvironmentincludingpre-operativeoptimisation

➢ PatientswithPHshouldideallybemanagedinspecialistcentres experiencedinthemanagementofpulmonaryhypertension

Acknowlegements

AnaesthesiaandCriticalCare- VickyWilson

PulmonaryVascularUnit–DavidKiely–CharlieElliot–RobinCondliffe–IanSabroe–Thanos Charalampopoulos–LisaMartinandIainArmstrong