JEmergTraumaShock.2012OctDec5(4):285295.

PMCID:PMC3519039
doi:10.4103/09742700.102357

Hemorrhagicshock:Thephysiologyapproach
FabrizioGiuseppeBonanno
TraumaDirectorate,ChrisHaniBaragwanathHospital,Johannesburg,SouthAfrica
Addressforcorrespondence:Dr.FabrizioGiuseppeBonanno,Email:f.g.bonanno@gmail.com

Received2011Mar3Accepted2011Apr13.

Copyright:JournalofEmergencies,Trauma,andShock

ThisisanopenaccessarticledistributedunderthetermsoftheCreativeCommonsAttributionNoncommercialShareAlike3.0Unported,which
permitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.

Abstract
Ashiftofapproachfromclinicstryingtofitphysiologytotheoneofphysiologytoclinics,with
interpretationoftheclinicalphenomenafromtheirphysiologicalbasestothetipoftheclinicaliceberg,anda
managementexclusivelybasedonmodulationofphysiology,isfinallysurgingasthesafestandmost
efficaciousphilosophyinhemorrhagicshock.ATLSclassificationandrecommendationsonhemorrhagic
shockarenothelpfulbecauseantiphysiologicalandpotentiallymisleading.Hemorrhagicshockneedstobe
reclassifiedinthedirectionofusefulnessandtimingofintervention:inparticularitsassessmentand
managementneedtobetailoredtophysiology.

Keywords:Classification,hemorrhagicshock,management

INTRODUCTION
IthasalwaysbeenpuzzlingtryingtounderstandandaccepttherationaleandbenefitsoftheATLS
classification[1]especiallyafterhavingreplacedHolcroftmoresensibleclassification,[2]asforthedifficulty
ofpracticalimplementationwithreferencetotimingandoptimalmanagement.Bothclassificationswere
consequencesofexperimentsdoneonanimalsthatdonothavethesameadrenergicreceptorsdistribution
andamountonhumans,whichfurthervariesfromindividualtoindividual,[3,4]andamisinterpretationof
Shiresstudiesinthe1960s,[5,6]deceptivelycorroboratedbytheimprovementinrenalfailurestatisticsinthe
Vietnamwarwiththeoverloadofcrystalloids,incidentalwithacoincidentalincreaseofARDS.[7,8]

Amoreusefulclassificationofhemorrhagicshock(HS),individualphysiologytailoredand
therapeutic/decisionmakingfriendly,whichisbasedontheabovetwoclassificationsofshock,hasbeen
elaborated.

CLASSIFICATIONOFHEMORRHAGICSHOCK
Classificationsaremeanttosummarizetheassessmentandmanagementofascenarioorofaproblem[
Table1].ATLSclassificationofhemorrhagicshock(HS)[1]isnotsensitiveandspecificenoughtohelp
decisionmakinginreferencetothetimingofmanagement,beingbasedonlyontheamountofbloodloss
thatmayormaynotberightlyestimated,anditisunhelpfulanddifficulttoapplytoo.[9]Theprevious
physiologicalclassification[2]hadadvantagesoverlookedandnotrecapturedbytheATLSone,namely
theprogressionoftheeffectsofahemorrhageonthedifferentorgansandsystems,amorereliableindicator
thantheamountofblooditselfinguidingtimingofintervention.Nevertheless,thephysiological
classification,despitebeingmorefunctionalandusefuldoesnotkeepinaccountthepreexistentdifferent
organphysiologicalreservesorcanforeseethelevelatwhichhypotension,crucialparametersignaling
decompensation,occurs.Byrecommendingthefluidloadof2Lcrystalloidsloadforadultpatientstotestthe
reliabilityofcompensatorymechanisms,asrecommendeduptorecently,classicalATLSguidelinesactually
delaythetimingofinterventionassourcecontrolwhentestingisnotrequiredandmorecruciallyendup
increasingtheongoingorspontaneouslystoppedbleeding.Theonlynoveltyoftheclassificationisthecutoff
at30%bloodlossaslevelofbloodlossalwaysmanifestingwithhypotension,persenotenoughuseful
informationtoguidedecisionmaking.

Thenewclassification[Table2],whichmaywellbecalledthe"physiologicalHSclassification"or
"therapeuticalHSclassification,isbasedonadecisionmakingthatkeepsinaccounthardpracticeandbasic
physiologicalconsiderations,suchasthesignificanceoffluidbloodresistanthypotensionandbodynatural
hemostaticmechanisms,therightdefinitionofshocknonethelesstherelevancethathemorrhagetriggeredIR
andSIRhaveincriticalillnessscenariosassecondaryinsultfromischemia.

Incriticalshock,infactthereisnomuchofcirculatingvolume,andbrainandheartinternalcirculationsare
barelyholdingasaresultofthesystemicvasoconstrictionfromchemoreceptorandcentralnervoussystem
receptorsstimulation,whileinsevereshockthereissufficientbloodvolumetopotentiallymaintain
perfusiondespiteendogenouscompensatorycapacityintermsofvasomotion/vasoconstrictionhasbeenlost
inmoderateshockcompensatorycapacityinsteadhasnotbeenlostandmildshockindicatesonlysome
bloodloss.

Thephysiologicaltherapeuticalclassificationmustbedistinguishedfromtheprognosticone,i.e.reversible
orirreversibleshockandimplicitlyphotographsthelevelsofshockwithinatimeframeofreversibility.It
mustalsonotbeconfusedwiththetwohitmodelofphysiologicaldeteriorationeither,whichdescribethe
timepeaksofclinicaldownfall.

RATIONALE:TIMINGOFINTERVENTIONTHERESUSCITATIONPARADOX
Timingiseverything.Themainstemoftreatmentofshockisremovalofthecausaprima(source
optimizationincardiogenicshock(CS),sourcecontrolinHS,andsourceeliminationininflammatoryshock
(IS).ThetimingfortreatmentofHScanbesummarizedinatherapeuticparadox:Intervenesooninavery
sickpatienttopreventdeathandacceptingtheinevitablecomplicationsimprovethehealthyormoderately
sickpatientbeforesurgerybyoptimizingorreinforcingpatientphysiologywithaviewtoreduceorprevent
complications.So,sickerthepatient,theearliermorerapidandaggressivetheinterventionhastobetheless
sickthepatientmoretimehastobetakenforimprovementbeforeintervention.Patientbiologicaland
physiologicalreserves(immunity,nutrition,exerciseandagerelatedcardiovascularreflexesandspecific
organshomeostaticautoregulatorycompensatorymechanisms),preexistingsystemicdiseasesor
derangements(chronicrenalfailure,hypertension,diabetes,chronicliverdisease,andchronicheartdisease),
andconcurrentdrugintake(alcohol,antihypertensive,antiarrhythmic,blockers,steroids,vasodilators,
inotrops,andinsulin)playdifferentsignificantrolesintheoverallprognosisofthecriticalillnessbydelaying
detection,limitingthephysiologicalreserveofthedifferentorgansandcomplicatingrecovery.

TimingofinterventionforsourcecontrolinHSdependsontheclinicalseverityanddegreeofcompensation
thatinnormalindividualsreflectsthelevelofbloodloss,andontheresponsetofluidsload.TBVis70ml/kg
bodyweightinadults,80ml/kgininfantageand8090ml/kginnewborns.HSattheextremesoflifeis
moreseriousthanattheageinbetweenasforthenotdeveloped(newbornsandinfants)orlessresponsive
(elderly)vascularreflexes.Elderlypatientsasamatteroffactcanhaveshockatseeminglynormalblood
pressureof120mmHgduetoatherosclerosis,hypertension,andlessfunctionalreflexesmaintaining
relativelyhighpressuresforperfusion.[10,11]

HSinpregnantwomendoesnotmanifestwithshocksignsuntil3035%TBVislostduetotheincreaseof
plasmaandcardiacoutput.Thesupinepositionneutralizestheadvantagesofthosepreparatorychangesto
forthcomingintravascularvolumelossesasfortheuteruscompressingontheIVCandimpairingVR,
phenomenonavoidablebyalwaysmaintainingaleftobliquepositioningwhenlyingdown.

Acutebloodlossandhypotensionwithbrainandheartdisturbancesorabloodloss>40%ofTBV(critical
HS,unstablyunstable)requirestandbysurgerytostopbleedingpersistinghypotensionnotrespondingto
bloodorfluidsload(severeshock)withstablenormalizationofsystolicandreversedHRtrend(stably
unstable),alsorequiresemergencysurgerytostopbleeding.

Heartandbraincirculationincriticalshockareholdingbecauseofstillfunctionalregionalvasomotion,but
theyhavealreadypassedthecriticalextractionpointasbydefinitionischemicsignsarealreadypresent.

Noresponsetosmallvolumesofhypertonic/colloidfluidloadinsevereshocksignifiesaderanged
vasomotionduetolossofendogenouscompensationasthebeginningofaphysiologicalslopewith
continuinghemorrhageatarateinwhichreflexcompensatoryvasoconstrictioncannotmaintainpressures.

Anythingelseotherthanafastruntotheaterandswiftanesthesiainductionwillkillpatientsintheabovetwo
scenarios.Topushextrafluidsfastoringreatquantitywilldisruptthebalancebycounteractinglifesaving
hypotension,vasoconstriction,vesselretraction,andclotformation,withtheendresultofkillingthepatient
orinthelesspessimisticscenariocausingheartattackoracerebrovascularaccident.[12]

Themechanismsaccountingfortheworseningofthesituationbeforeorintheabsenceofsourcecontrolin
criticalandsevereHSaremultipleandactincombinationevolvinginaviciouscircleofacceleratedexitus.

ThechemoreceptorresponsetolowPaO2atlevelsofpulsepressureof7080mmHgincreasesBPbydirect
stimulationofthevasomotorcentersinthereticularactivatingsubstanceofthemedullaoblongataandlower
pons,increasingarteriolestoneviasympatheticnervoussystemstimulation.Atsomestage,withoutorbefore
sourcecontrolandinthepresenceofsupplementaryfluidsandoxygenorhyperoxia,thevasoconstricting
reflexgetsdampenedeventually,withHbO2reducedtominimaltermsfromtheunarrestedbleedingandCO
reducedfromthedecreasedvenousreturn,andwithdissolvedPaO2thatcannotsustainCaO2atalevelto
maintainsufficientperfusion(DO2),thereflexgetstriggered.Bythetimethechemoreceptoristriggered
though,HbO2willhavereachedminimallevels,andsotheDO2,andbrainandheartarealreadysufferingof
relativehypoxia(criticalshock).CoronarieshaveaveryhighO2ERatbasalconditions(75%vs.25%of
mostoftheotherorgans)andarealreadyinpathologicalsupplydependenceincriticalshock,dangerously
nearthecriticalextractionlevelbeyondwhichanaerobicmetabolismandpotentiallydevastatingfurther
ischemiaensues.[13]Adjunctivehyperoxiawillparadoxicallyacceleratethephysiologicalslope,particularly
ifcombinedwithbloodorfluidsincreasingbleedingratebeforesourcecontrol.

Asimportantly,theischemicCNSresponsetopressures<60mmHgwithdecreasedDO2delivery,as
signaledbyanalreadyclinicallyimpalpablelevelofsystolicpressure,wouldalsobecounteractedbyfluid
administrationwiththeparadoxofhavingasituation,otherwisekeptcompensatedbythetworeflexes,being
insteaddecompensatedbyfluidsandoxygenadministration.

Moreover,theincreaseofintravascularvolumeswithfluidtransfusionbeforesourcecontrolpreviously
advisedwouldfurtherdecreaseperfusionasitcounteractsthethreenaturalphysiologicalmechanismsof
hemosthasis,i.e.arterialretraction/spasm,hypotension,andclot,endingupincreasingbleedingand
decreasingpressures.

SinceWorldWarIinfactithasbeenknownthat:hypotension,vasoconstriction,vesselretraction,andclot
formationpreventedcontinuationofbleedingafterwoundingbloodorplasmatransfusionbeforesurgery
wasawastedresourcethatcouldcauserebleedingandsurgerywithcontrolofhemorrhagewasthemost
effectiveresuscitation.Theinsightofwarsurgeryexperiencehadtoldusthathypotension,clotformation,
andvesselsretractionwerethereasonsforpatientssurvivalafterarterialdamageorinjury,thatanuntreated
arterialinjuryorkilledrapidlyorwassavageableifspontaneouslystopped,whileavenousinjuryhadtorely
onlyonclotformationtostop.Thisimplies,paradoxically,thatmajorvenousinjurycanbemorelethalthan
arterialoneinsitessuchasmediastinumandretroperitoneumwhereitcannotbecompressed.[1417]

Thus,pushingfluidsandhyperoxiaandthemaintenancethoughtemporaryoftheactualmeanarterial
pressure(MAP)incriticalshockandsevereshockbeforesourcecontrol,isinprincipleanddefacto
deleterioustopatient'sphysiologyandoutcome.Delayandstandardresuscitationwithoxygenandfluids
willparadoxicallyresultinanearlierischemiaofthetwoorgansthantheonethatwouldoccurifno
transfusionandearlysurgerywereinsteadimplemented.

Thefluidloadtestisconsequentlyawastefulanddamagingexerciseincriticalhemorrhagicshockasisany
delaytofastsourcecontrol.

Inallothercasesofhypotensiveshockwithnoheartorbrainischemiathefluidloadtestshouldbecarried
outasittellsusonthestatusofcompensationpresentand,importantly,allowsdistinctionbetweensevere
andmoderateshock,i.e.betweenarushtotheaterortemporizingonfurtherdiagnosticortherapeutic
strategies.Hypotensiveshockwithoutheartorbraininvolvement,independentlywhetherthelossis20%
(notalwaysaccompaniedbyhypotension)or30%(alwaysaccompaniedbyhypotension)ofTBV,which
respondstoblood/fluidsoverloadtestwithnormalizationofbloodpressureandreversetrendintachycardia
(moderateshock),indicatesreliablythepresencestillofacertainphysiologicalreserveintermsof
compensatorymechanisms.Suchscenariosdonotrequireimmediateorrapidsurgerybutcanbeinvestigated
beforesurgeryorinterventionalradiologyandconsideredforconservativemanagement.Noinvestigation
shouldbeentertainedinthepresenceofcriticalorsevereshock.

Investigationsshouldbeallowedonlyinnothypotensive,compensatedmildtomoderateHS,andshouldbe
aimedonlytoidentifytheoriginofthebleeding/sandconcomitantpathologiesworthyoressentialtobe
pickedupbeforesurgery.History,clinicalassessment,logisticsandequipmentdictatethetimingof
interventionandinvestigationsincompensatedshockorconsiderationforconservativenotoperative
management.Bloodtransfusioninthesenotemergencycasesshouldbegivenwithinmaximum46hfrom
insulttopreventIRcomplications,tillaleveljudgedsatisfactory(Hb7g/dLwithHct>2124%)in
healthypatientsand910mg/dLwithHct2730%incardiacpatients,keepinginaccountSvO2minimal
levelsof70%,andnormalizedvaluesofBEandLAintheabsenceofinfection.[18,19]

ModerateHSrespondswelltocrystalloidsandPRBCi.v.mildshockcanbetreatedwithoralfluids,ori.v.
fluids.

Forstabilizationtobeconsideredestablished,besidesnormalBPandreverseornormalpulse,patientsmust
beseenwithnormalorimprovedcomplexion,mentalstatus,urinaryoutput,andcomfortingindirectsignsof
perfusionsuchasPaO2andSaO2.

PITFALLSINHEMORRHAGICSHOCKRESUSCITATION
Theloadingfluidtestof2LofcrystalloidspreviouslyrecommendedbyATLSwasdefacto
antiphysiologicalanddeleteriousespeciallywhenindiscriminatelyimplementedanddidnotbringincreaseof
survival,[20]butanincreaseinmortalityandpostoperativecomplicationswhencomparedtonofluidsor
lessfluidsresuscitation.[2124]Experimentalevidenceconfirmedthedeleteriouseffectsofthecrystalloid
bolus.[25,26]

Atnormalheartconditionsandhealthyvalvesandmyocardium,anyincreaseofvenousreturnwill
effectivelyincreaseMAPwhichwillincreaseactualbleedingbycounteractinghypotension,the
physiologicalvasoconstriction,andtheclottingattempts,whicharethethreenaturalmechanismsthe
organismusestostophemorrhage.Vasodilatationanddecreasedviscosityfromhemodilutionalsotriggerthe
samechainofevents,leadingtoincreased,continuousorrecurrentbleeding.Theseconsiderationsand
observationsweretestedinanimals,[2536]humans,[2022,37,38]andcomputersimulations[39]and
confirmedthat(i)toomuchfluidinfusioncauseshemodilutionofplateletsandclottingfactors,increaseof
bloodpressure,decreaseofbloodviscosity,vasodilatation,allfactorsthusleadingtoablowoutofthe
hemostaticplugwithaccentuationofongoinghemorrhageor/andsecondaryhemorrhage(ii)bloodloss
causeshypothermia,whichcausescoagulopathy(iii)inpatientswithpenetratingtrunkinjuryand
hypotensionanduncontrolledvascularinjury,ifnofluidsinstandardfashionaregiveninprehospitalsetting
beforetheater,survivalisincreased,complicationsdecreasedandhospitalstayshortenedcomparedto
standardfluidresuscitation(iv)surgicalhemosthasisisthekeytherapeuticactforuncontrolledhemorrhage
and(v)limitedormoderateresuscitationissuperiortoaggressiveresuscitationinuncontrolledvascular
injury.Samehemodynamicandhemostasisderangementsoccurifhypertonicsalineinsteadofcrystalloidsis
used[Figure1].[2527,30,3334,36]

Moreover,theprinciplefirstcrystalloidsthenblood,evenworseina3:1ratio,wasbasedontheassumption
thatnoncorpuscolatedplasma,thefluidpartofplasma,hasfirsttoreplacetheinterstitialintracellularshifts
occurringduringhemorrhage.Shiresstudies[5,6]wereaccurateontheassessmentoffluidsshifts,notinthe
waytomanagethem.Thehomeostasisofwaterbidirectionallyinthecellinterstitiabloodpathwayswillbe
obviouslyderangedinnotcompensatedshockwherebydefinitionthegrasponmaintainingbloodpressure
byarteriolarvasoconstrictionfailsandtheratiosintheStarlingequilibriuminthecapillariesdefault.Itis
intuitivethatonlybyrestoringvasoconstrictioncapacitytheshiftscanreoccur.Thisassumptionwasmissed
whenthe3:1ratiowaspostulatedastherightone,confirmingtheneedtocategorizeshockforany
experimentorstudyinamorephysiologicalmanner.TherealmessagefromShiresworksisthat
replenishmenttobeeffectiveandaccuratecanonlybedoneaftersourcecontrolwherethesolutionof
continuityisrepairedandcompensatoryphysiologyrestored.Onlythenfluidsinfusionwillequilibratethe
threefluidcompartments.Itistruethatcombinationsofcrystalloids,plasma,andbloodintheVietnamwar,
increasedsurvivalanddecreasedrenalfailureatexpensesofARDS(formerDaNanglung),butthatcannot
beattributedtothecombinationfluidsblood3:1morethatitcanbeattributedtobloodonly.[7,8]Theratio
3:1isnotonlyinaccurateinitsconception,amountandpriorityoftransfusionbutalsoforitsindiscriminate
use,i.e.whethershockiscompensatedandwithorwithoutsourcecontrol.Moreover,patientsselectionwas
notdoneintermsofcategorizingthemwithdifferentclassesofshockandthedecreaseofrenalfailureis
likelytohaverepresentedanaturalselectionoccurredinsurvivorswithnotcritical/severeshockcases,
eventuallysomeofthemevolvinginARDS.Besidesthenegativeeffectsonbleedingandonviscosityof
microcirculation,theclassicalapproachdoesnotmakesenseintuitivelyeither.Ifbloodlossistheprimitive
derangement,itisexpectedbloodreplacementtobethemainandmostimportantcorrectiveaction.Inother
words,bloodshouldbegivenfirstandcrystalloidsshouldfollowoncethefluidcomponentoftheplasma
shiftstowardinterstitialintracellularspacesandincreasesbloodhematocrit.[40]Theinfusionofcrystalloids
wouldthenreplacethelostintravascularcomponentandrestorehematocrit.Itissimpledeductionthatunless
thereisalossofcontinuityleftunrepairedinthecirculationsystem,whichisaclosedsystem,anyfluidshift
fromcellstointerstitiatointravascularspacewouldbereversedintheoppositedirectionbyreproducingthe
dynamicsbackwards(ClaudeBernardhomeostasisconcept).Inhemorrhageitisbloodthatislostandblood
needstobereplaced,atleasttominimumphysiologicallevelswhenbloodlosstrespassesthem.Anindirect
advantageofthisshiftofpolicywouldbetheshorteningoftimeofclotformationcomparedtothefirstfluids
thenbloodcurrentpolicythathasdominateddecadesofpracticeintraumawithdeleteriouseffects.[41]

InhypotensiveshockRinger'slactateshouldthereforebeusedonlyafterbloodorbloodcomponentstherapy
inanamounttailoredtobalanceosmolalityelectrolytesandhemathocrit.

AnotherdrawbackofanexcessoffluidtransfusionisRV/LVcardiacfailureorCSifthetwohalvesofthe
hearthavepreexistentdecreasedfunctionalreserveduetovalvularormyocardialpathology.Two
problemswouldthenbefacedoverloadandlowcardiacoutputwithtreatmentofoneconditionworsening
theotherone[Figure2].Directinotropicsupportwouldthenberequiredinconjunctionwithblood
replenishmentandaggressiveICUmonitoringofthecardiacoutput.

Furthermore,excesstreatmentwithfluidorbloodoverloadisdeleteriouswhetheriseffectedbeforesource
controlorafterwards,asitmaycausesecondaryintraabdominalcompartmentsyndrome,[4244]with
changesthattriggerasecondhitSIRorIRsyndromesandALIhelpedbySIRandvasodilatation,if
resuscitationisdonelate,orworsenedbyvasoconstrictionwithseriouseffectsonabdominalorgans
perfusion,ventilation,kidneyfunctionandvenousreturn,ifresuscitationisdoneearlyandinexcess.Gut
edemaandincreasedintraabdominalpressuretillabdominalcompartmentsyndromelevelwillensue,duethe
increaseofcapillarynetfiltrationpressure(cNFP)secondarytoincreasedintracapillarypressureresultofthe
increasedpressureupstreamfromincreasedvolume.Starlinglawrulingthepermeablecapillariesnet
filtrationpressurestates:NFP=[capillarypressure(interstitialfluidpressure+plasmacolloidosmotic
pressure)+interstitialfluidcolloidosmoticpressure].

InadequateordelayedresuscitationistheothersideofinappropriatetreatmentofHS.Cardiacarrestcan
occurasaprimaryhitforinsufficientvenousreturnandcoronaryischemiaduetothedependenceof
coronaryperfusionfrombloodflowduringthediastolephase,whichisdecreasedfollowingthedecreaseof
thestrokevolume.Thecompensatorytachycardiaonlyworsensthesituationacceleratingheartischemia.
PostHSSIRorIRphenomenonisthesecondseriousconsequenceofinadequateordeficientresuscitation
leadingtoincreasedmorbidityandmortality.[45,46]

STRATEGIESANDTACTICS

Adjunctsintreatment

CompensationofHSoccursbyreflexarteriolarvasoconstrictionsympatheticmediatedwithcatecholamines
actingon1receptors.Atsomestagehyporeactivitytoendogenouscatecholaminesinstalls,signaling
decompensation,whichbecomesparalysiswhenacompletelackofresponsivenessoccursevento
exogenousvasoconstrictorssignalingirreversibleshock.

Besidesitsprovenbenefitsinsepticshock(SS),vasopressinaliasargininevasopressin(AVP)aliasanti
diuretichormone(ADH)hasshownbeneficialeffectsinCSandincardiacarrest.[4751]InHSAVPhas
beenfoundtoreducethefluidrequirementandimproveneurologicaloutcomeandcardiopulmonary
parameters.[52]Vasopressinasbolus(0.4Uonceortwice)and/orinfusion(0.040.1U/min)reverses
intractableorprolongedhypotensioninthelatephaseHSorintraoperativeHSwithandwithoutcardiac
arrest.[5359]VasopressinvasoconstrictiveeffectresultsfrominhibitionofKATPchannelsandinhibitionof
nitricoxideinducedaccumulationofcGMP.Replacementofdepletedstoresofvasopressininthe
neurohypophysismayalsocontributetoreversalofshock.[60]ADHmaycauseproblemsathigherdosages
orwhengivenforseveralhours.[61]

Noradrenaline(NE)isapotentalphaadrenergicagonistwithminimaladrenergicagonisteffects.NE
increasesMAPduetoitsvasoconstrictiveeffectswithlittlechangeintheheartrateandstrokevolume,and
bydoingsoincreasesindirectlythecardiacoutputaswell.DosesofNEgoingfrom0.2g/kg/mintitratedto
responseupto3.3g/kg/minareusedtomaintainCOandBP.Itsdrawbacksareanincreaseofworkload
andoxygenconsumptionpluscoronaryvasoconstriction.NEshouldbeusedearlyasneurohormonal
augmentationtherapysupportinghemodynamicfunction,ratherthanasalaterescuetherapytotreatshock.
[62]

BothNEandADHcombinedwithhydroxyethylstarchimprovecerebralperfusionpressure,oxygenation
andmetabolisminHS,withAVPbeingthefasterofthetwo.[63,64]ThecombinationAVP+NEisan
effectivetreatmentforuncontrolledHSattheearlystageafterhemostasis,ifbloodisunavailable.[65]

NEshouldbeaddedtoAVPifthelatterisineffective,andmustbediscontinuedbeforeADH.[66]

LikewiseinSS,thecombinationoflowdosesNEandADH,orADHonitsown,canbeadministeredfrom
presentationandcategorizationofcriticalorsevereHStillbeforesourcecontrolasavasoconstriction
maintaining,vasomotorcollapsedelaying,drug.

Oncearterialpressureisbroughttoasystolicofatleast90mmHgandaMAP>6570mmHg,andCOstill
wouldbelow,intravenousdobutaminemaytakeover.Innormalheartsthereishoweverscarceneedfor
inotropicsupportinthepostoperativeICUphase.

Dopaminemayalsobeusefulinpatientswithcompromisedsystolicfunction,lowCO,andMAP.Atdoses
ofapproximately1020g/kg/min,theprevailingadrenergiceffectleadstoarterialvasoconstrictionand
elevationinbloodpressure.Theproblemwithdopaminehoweveristhatbeforethecardiovascularsystem
respondstovasoconstrictinghighdosagesithastopassthroughlowandmediumconcentrationsthatmay
temporarilyworsenthesituationbyincreasingtheheartrateandregionalvasodilatationinamomentwhere
thereisnotmuchbloodincirculationfurthermoredopaminepredisposestodysrhythmias.

Titratedhypotensiveresuscitation

Toolate,toolittle,tooearlytoomuch,toolateandtoomuchareallharmfulresuscitationstrategies.To
whichlevelthenshouldresuscitationbemaintainedbeforeimminentsurgeryortemporarilybeforesurgeryor
astheonlytreatmentifaconservativenonoperativeapproachisadopted?Thisshouldbealevelofblood
pressuresufficientenoughtomaintainperfusionwithoutriskingeithercontinuationofbleedingorre
bleeding.ThesetargetsarereachedwithTitratedHypotensiveResuscitation[Table3].

HypotensiveresuscitationisanoldconceptintroducedbyCannonaroundtheFirstWorldWar,[1417]but
implementedonlybyCrawfordinlate1980sforthetreatmentofrupturedabdominalaorticaneurysmbefore
surgery,[38]recentlyreintroducedas"permissiveortitratedhypotension"bytheIsraeliDefense
Force[67,68]fortransportedpatientswithHSwhereresuscitationmonitoringandtitrationaredifficultto
achieveandasmallvolumeofinfusionislogisticallyconvenient.Thesystolicpressurewaskeptlessthan90
mmHgtomaintainaconsciousnessleveloratthepalpablepulselevel,i.e.70and<90mmHgbytitrated
prnhourlybolusof250mlofRLorHTSskincomplexionandconsciousnessleveldirectresuscitationina
consciouspatient.

Thepresenceofassociatedheadinjurythatisnotmild(GCS12)compoundstheclinicalpicturebecause
ofthedifficultyorimpossibilitytouselevelofconsciousnessasanindicatorofthelevelofbloodlossand
compensatorymechanismsefficacy,andtheunpredictablelossofthecapacityofflowselfregulation
followingtrauma.PatientswithHSandHIneedthereforeamoderateresuscitationinbetweenpermissive
hypotensionandstandardresuscitation,i.e.systolicof100mmHgparticularlyinviewofthefactthatthe
brainlosesitscirculationselfregulatorycapacityatvariablelevelsofHI.[69,70]
Experimentalevidenceandclinicalexperienceincivilianandmilitarysettinghaveshownbenefitsandsafety
ofbolusesof250mloffluids,whethercrystalloids,colloids,orhypertonicsalineatdifferentconcentrations,
aseffectiveandsafeinitialmanagementofpatientswithHS[67,68,7173]HTSshouldbegivennotmore
than250,maximum375,ml/htomaximizeitsmeritsanddiminishitsdrawbacksonbleedingbyinterference
withcoagulationandmoreimportantlyfollowingincreaseofpressureasdirecthemodynamiceffect.

Inarecentstudyonhumans,thenodifferenceofmortalityinpatientswhoreceivedeitherHTS7.5%
Dextran70at6%orHTS7.5%administrationbolusesof250mlcomparedtoNS0.9%250mlasinitial
fluidtreatmentbeforesourcecontrol,[74]associatedtoanincreaseofmortalityinthesubgroupwhodidnot
receivebloodtransfusioninthefirst24h,appearstocontradictsomeoftheconclusionsofprevious
experiences.Theinclusion,inthestudy,ofpatientsinHSwithSBP70mmHgorwithSBPbetween70
and90mmHg+HR110bpmwouldfittheprofileofcriticalandsevereshockcategoriesifbrainorheart
wereinvolvedandaknownloss<40%hadoccurred,ornoconsistentresponsetothefluidboluswasnoted
moreover,theobservationsmadeinthegroupwithnobloodtransfusionindicatepatientsinwhomtypeand
amountoffluidswouldnothavemadedifference.Thestudyonlyemphasizestheneedofamoreaccurate
andusefulcategorizationofHS.

Hypotensiveresuscitationandpermissivehypotensionondemandortitratedhypotension,more
accuratelyTitratedHypotensiveResuscitation(THR),remainstheidealresuscitationandthewaytogoas
standardinitialresuscitationparticularlyduringtransportofpatientswithcriticalorsevereHSindependently
onthescenario,whethercivilorruralormilitary.

Emergencyprotocols:Thephysiologyapproach

IncriticalshockwithaknownTBVlossof40%orthepresenceofbrainandheartischemicchanges
thereisnoproveneffectivestrategyofresuscitationoutofhospitalthatwouldnotcontemplateheroicslikein
situextremeoutdoorresuscitation(EOR)bysmalloperativeunitswithorwithoutsuspendedanimation
fastlyinducedhypothermiatechniques.SuchtechniqueswithportablefemorofemoralCPBP/ECMO
withouthypothermiahavegivendismalresultsoutdoorsinCAorCSbeforerefractoryCAinnormovolemic
notexhanguinatingpatientsevenwhenappliedwithbeatingheart,andasurvivalof2030%indoors.[7576]
IntraumascenarioswithsolutionofcontinuityinthevasculartreeanddecreasedbloodvolumeEORwith
themethodofsuspendedanimationcanonlybeeffectivewithhypothermiainducedbycoldsalineaortic
flushviaemergencysternotomy/thoracotomy.[77]

UntilmethodsandtechniquesofEORandsuspendedanimationhypothermiaareoptimizedorperfected,
onlythreeoptionsaresofaravailable.Oneisalifesavingruntothenearestmedicalfacilityforrapid
sourcecontrolwithcontinuousbloodtransfusionrunninginhighcapacity/flowcannulae,wellknowingitis
destinedtogetlost.Twoistorunatthenearestmedicalfacilitywithnofluidtreatmentwhatsoeveratall
leavingtothepatientnaturalbalancingmechanismstodotheirbestwithoutiatrogenicinterferenceuntil
rapid/swiftanesthesia/surgeryforsourcecontrol."Three"isTHR.Intheauthor'sviewnoresuscitationor
THRarethemostsensibleoptionstouseasinitialresuscitationbeforesourcecontrolinpatientswith
hypotensiveHSbothindoorandoutdoorwhilerushingonthewaytoamedicalfacility.Thenoresuscitation
optionmayindeedbethebestoption.[21]

THRshouldalsobeusedinsevereHSaftertheinitialbolusofthefluidloadtestdiscriminatesitfromthe
moderateoneifshockturnsouttobemoderatewithnormalizedsystolicandreversedtachycardiatrend,no
furtherfluidshouldbegivenuntilsourcecontrol.

WhichfluidtouseincriticalHSinprehospitalphaseandwhichfluidshouldbeusedforloadtestin
severeHS?

Itshouldbethefluidonewouldliketouseasbridgeinfusionuntilsourcecontrolifbloodwereunavailable:
hyperosmotichyperviscoussolutions(HHS),HTSorRLcombinedwithalginates,andconjugatedalbumin
solutionsappearsofartobeexcellentchoice.Thereisoverwhelmingevidenceontheimportanceof
maintainingmicrocirculationfunctionwithaimtooptimizeperfusioninHSbyusingaptfluidwithspecific
characteristicsandcomposition,particularlyviscositymorethancolloidosmoticandoncoticproperties,and,
inparallel,ontheirreplaceablefunctionofbloodfrommicrohemodynamicsandoxygentransportend
points.[7894]
ToshowpredictablebenefitsofTHRonmortalityandmorbidity,[85,95]specificallyinpreventingthe
installingofcrypticshockabuttinginaIRMOD/Sclinicalpictureinthepostoperativeperiod,trials[96]
shouldbedoneonpatientsinhypotensiveshockclassifiableassevereorcritical.[97]

Itisunderthesameprincipleoftheleastinterferencewithphysiologyduringresuscitationsthattacticsand
strategiessuchasTHR,damagecontrol,anddamagecontrolresuscitation,havebeenconceptualized.
Likewisegeneralanesthesiashouldtoobetitratedtopain/autonomicstimulationresponse(autonomic
controlledanesthesia)underthecomprehensiveconceptofphysiologyapproach.

Etomidate,S(+)ketamineoralfentanylinductionandS(+)ketamineorremifentanylcontinuousintravenous
anesthesia(CIVA)titratedtoresponseistheauthor'ssuggestedmethodforanesthetizingcriticalandsevere
shockpatients.[98100]

EmergencyprotocolsbasedonaPhysiologyapproachcomprehensivestrategy,i.e.theTherapeutical
ClassificationofHS,THR,exogenousvasoconstrictivesupport,autonomiccontrolCIVA,andblood
andbloodcomponentsreplenishment,[101108]aresuggestedinTables4and5.Inhypotensiveshock
Ringer'slactateshouldbeusedonlyafterbloodorbloodcomponentstherapyinanamounttailoredto
balanceosmolalityelectrolytesandhematocrit.

CONCLUSIONS
ThestandardATLSclassificationofHSisunhelpful,confusingandmisleadingasitfocusesontheamount
ofbloodlossinsteadofindividualphysiologicalresponsetohemorrhage,whichisthecorebydefinitionof
thederangementwecallshock.Anewclassificationwasneededandcenteredonphysiologylikethe
classicalclassificationofHolcroftemphasized.

Theeraofflatanestheticsandsurgeryisoveranditistimewegotowardatailoredtoindividualphysiology
restorationandreprioritizeallcriticalillnessmanagementfromthemicrocirculationstandpoint.

Fluidsasfirstmodalityoftreatment,particularlyinexcessasrecommendedtillrecently,aredeleteriousin
hypotensiveshockandshouldbeconsideredsecondlinemodalitymoreovershouldbegivenafterblood,
andinanamountbasedonadjustingosmolarity.

Exogenousvasoconstrictorsareavalidtherapeuticstrategyonceendogenousvasoconstrictionhasfailedto
maintainthegripontheflowcontrollingarterioles.

SavelifeistheCommandmentindecompensatedhypotensiveshocknotrespondingtofluidloadtestor
withacalculatedTBVloss>40%orwithbrainheartsignsofischemia,acceptinginevitableandobligatory
IRandaphaseofCrypticShock.

Preventcomplications,namelyIR,istheCommandmentincompensatedmildormoderateshock.

Playingwiththeenemyinitsownwayisthekeywordofthegame.Donotalterthephysiological
compensatorymechanismsbutkeepthemandreinforcethem.Letthebodyruntheorchestraandfollowit.

WithouttherightconvenientandphysiologicalclassificationofHS,wewillstillcontinuetogenerate
controversiesandcontradictoryinvestigatorappeasingresults.

Footnotes
SourceofSupport:Nil.

ConflictofInterest:Nonedeclared.

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FiguresandTables

Table1
Classicalclinicalclassificationsofhaemorrhagicshock

Table2

Therapeutical/physiologicalclassificationofHSandfirstlinemanagementofsourcecontrol

Figure1
EffectsofVRmanipulationsonhaemodynamicsinpatientswithnormalcardiacreserve

Figure2

EffectsofVRmanipulationsonhaemodynamicsinpatientswithdiminishedcardiacreserve
Table3

HS:toomuchtooearly,toolittleandtoolate.Whatistheidealorperfectresuscitation?

Table4

DecisionmakinginCriticalHS:Acomprehensivemanagement

Table5
DecisionmakinginSevereHS:Acomprehensivemanagement

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