Effects of vasopressinergic receptor agonists on sublingual microcirculation in norepinephrine-dependent septic shock.docVIP

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Effects of vasopressinergic receptor agonists on sublingual microcirculation in norepinephrine-dependent septic shock.doc

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Effects of vasopressinergic receptor agonists on sublingual microcirculation in norepinephrine-dependent septic shock

Morellietal.CriticalCare2011,15:R217 /content/15/5/R217 RESEARCH OpenAccess Effectsofvasopressinergicreceptoragonistson sublingualmicrocirculationinnorepinephrine- dependentsepticshock AndreaMorelli1*?,AbeleDonati2?,ChristianErtmer3?,SebastianRehberg3,TimKampmeier3, AlessandraOrecchioni1,AlessandroDiRusso1,AnnaliaD’Egidio1,GiovanniLandoni4,MariaRitaLombrano2, LauraBotticelli2,AgneseValentini2,AlbertoZangrillo4,PaoloPietropaoli1andMartinWestphal3 Abstract Introduction:Thepresentstudywasdesignedtodeterminetheeffectsofcontinuouslyinfusednorepinephrine (NE)plus(1)terlipressin(TP)or(2)argininevasopressin(AVP)or(3)placeboonsublingualmicrocirculationinseptic shockpatients.Theprimarystudyendpointwasadifferenceof≥20%inthemicrovascularflowindexofsmall vesselsamonggroups. Methods:Thedesignofthestudywasaprospective,randomized,double-blindclinicaltrial.NEwastitratedto maintainmeanarterialpressure(MAP)between65and75mmHgafterestablishmentofnormovolemiain60 septicshockpatients.Thereafterpatients(n=20pergroup)wererandomizedtoreceivecontinuousinfusionsof eitherTP(1μg/kg/hour),AVP(0.04U/minute)orplacebo(isotonicsaline).Inallgroups,open-labelNEwasadjusted tomaintainMAPwithinthresholdvaluesifneeded.Thesublingualmicrocirculatorybloodflowofsmallvesselswas assessedbysidestreamdark-fieldimaging.Allmeasurements,includingdatafromrightheartcatheterizationand norepinephrinerequirements,wereobtainedatbaselineand6hoursafterrandomization. Results:TPandAVPdecreasedNErequirementsattheendofthe6-hourstudyperiod.Thedataaremedians (25thand75thinterquartileranges(IQRs)):0.57μg/kg/minute(0.29to1.04)vs.0.16μg/kg/minute(0.03to0.37)for TPand0.40μg/kg/minute(0.20to1.05)vs.0.23μg/kg/minute(0.03to0.77)forAVP,withstatisticalsignificanceof P0.05vs.baselineandvs.placebo.Therewerenodifferencesinsublingualmicrocirculatoryvariables,systemic hemodynamics,oxygentransportandacid-basehomeostasisamongthethreestudygroupsduringtheentire observationperiod.Theproportionsofperfusedvesselsincreasedinrelationtobaselinewithinal