REVISTA
BRASILEIRA
DE
ANESTESIOLOGIA
PublicaçãoOficialdaSociedadeBrasileiradeAnestesiologia www.sba.com.brMISCELLANEOUS
Deep
versus
moderate
neuromuscular
block
during
one-lung
ventilation
in
lung
resection
surgery
Javier
Casanova
∗,
Patricia
Pi˜
neiro,
Francisco
De
La
Gala,
Luis
Olmedilla,
Patricia
Cruz,
Patricia
Duque,
Ignacio
Garutti
HospitalGregorioMara˜non,Madrid,Spain
Received27October2015;accepted1December2015 Availableonline28April2016
KEYWORDS
Neuromuscularblock; One-lungventilation; Lungresection surgery
Abstract
Backgroundandobjectives: Neuromuscularrelaxantsareessentialduringgeneralanesthesia
forseveralprocedures.Classicalanesthesiologyliteratureindicatesthattheuseof neuromus-cularblockadeinthoracicsurgerymaybedeleteriousinpatientsinlateraldecubitusposition inone-lungventilation.Theprimaryobjectiveofourstudywastocomparerespiratoryfunction accordingtothedegreeofpatientneuromuscularrelaxation.Secondary,wewantedtocheck thatneuromuscularblockadeduringone-lungventilationisnotdeleterious.
Methods:A prospective, longitudinal observationalstudy was made in which each patient
served as both treated subject and control. 76 consecutive patients programmed for lung resectionsurgeryinGregorioMara˜nonHospitalalong2013whorequiredone-lungventilationin lateraldecubituswereincluded.Ventilatordata,hemodynamicparameterswereregisteredin differentmomentsaccordingtotrain-of-fourresponse(intense,deepandmoderateblockade) duringone-lungventilation.
Results:Peak,plateauandmeanpressuresweresignificantlylowerduringtheintenseanddeep
blockade.Besidescomplianceandperipheraloxygensaturationweresignificantlyhigherinthat moments.Heartratewassignificantlyhigherduringdeepblockade.Nomechanicalventilation parametersweremodifiedduringmeasurements.
Conclusions:Deepneuromuscularblockadeattenuatesthepoorlungmechanicsobservedduring
one-lungventilation.
©2016SociedadeBrasileiradeAnestesiologia.PublishedbyElsevierEditoraLtda.Thisisan openaccessarticleundertheCCBY-NC-NDlicense( http://creativecommons.org/licenses/by-nc-nd/4.0/).
∗Correspondingauthor.
E-mail:[email protected](J.Casanova). http://dx.doi.org/10.1016/j.bjane.2015.12.002
PALAVRAS-CHAVE Bloqueio
neuromuscular; Ventilac¸ãoseletiva; Cirurgiaderessecc¸ão pulmonar
Bloqueioneuromuscularprofundoversusmoderadoduranteaventilac¸ão
monopulmonaremcirurgiaderessecc¸ãopulmonar
Resumo
Justificativaeobjetivos: Os relaxantes neuromusculares são essenciais durante aanestesia
geralpara váriosprocedimentos.A literaturaclássicadeanestesiologia indicaqueousodo bloqueioneuromuscularemcirurgiatorácicapodeserprejudicialempacientesposicionados emdecúbitolateralcomventilac¸ãoseletiva.Oobjetivoprimáriodesteestudofoicomparara func¸ãorespiratóriadeacordocomograuderelaxamentoneuromusculardopaciente.O obje-tivosecundáriofoiverificarqueobloqueioneuromuscularduranteaventilac¸ãoseletivanãoé prejudicial.
Métodos: Estudoobservacional,prospectivoelongitudinalnoqualcadapacienteserviucomo
indivíduo deestudoe controle.Foramincluídos 76 pacientesconsecutivos,agendadospara cirurgiaderessecc¸ãodopulmãonoHospitalGregorioMara˜nonaolongode2013,submetidosà ventilac¸ãoseletivaemdecúbitolateral.Osdadosdoventiladoreosparâmetroshemodinâmicos foramregistradosemdiferentesmomentosdeacordocomarespostaporsequênciadequatro estímulos(bloqueiointenso,profundoemoderado)duranteaventilac¸ãoseletiva.
Resultados: Aspressõesdepico,platôemédiaforamsignificativamentemenoresduranteos
bloqueios intenso e profundo.Alémdisso, complacência esaturac¸ãoperiféricade oxigênio foram significativamente maioresnesses momentos. A frequência cardíaca foi significativa-mentemaiorduranteobloqueioprofundo.Nãohouvealterac¸ãodosparâmetrosdaventilac¸ão mecânicaduranteasmensurac¸ões.
Conclusões: Obloqueioneuromuscularprofundoatenuaamecânicapulmonardeficiente
obser-vadaduranteaventilac¸ãoseletiva.
©2016SociedadeBrasileiradeAnestesiologia.PublicadoporElsevierEditoraLtda.Este ´eum artigo OpenAccess sobumalicenc¸aCCBY-NC-ND( http://creativecommons.org/licenses/by-nc-nd/4.0/).
Introduction
Ingeneral,theuseofneuromuscularrelaxants(NMRs)during surgeryrequiring general anesthesiahasbeen justifiedby theneedtoinducetotalmuscleparalysisinordertoavoid undesirable patient movements that could pose a hazard for correct surgical maneuvering, and toensure optimum conditionsforendotrachealintubation.
Anesthesiainlung resectionsurgeryrequirestheuseof NMRstoavoiddiaphragmaticmovementsorreflexcoughing thatcancausepotentiallydangeroussituations,particularly whenthesurgeonismanipulatingvitallungstructuressuch asbronchi, vesselsor nerves. On the other hand, correct positioningofthe double-lumentube mustbe checkedby introducingthefibrobronchoscopethrougheachlumen,and thisalsomaycauseunexpectedpatientmovements, includ-ingcough.Theaspirationofsecretions(acommonpractice inthesepatients)likewisemaygiverisetoundesiredpatient movements. On the other hand, routinelung recruitment maneuveringinsurgeryofthiskindrequirestheuseofNMRs tofacilitateopeningofthecollapsedlungregions.
However,theclassicalanesthesiologytextsindicatethat the use of NMRs in this type of surgery may be harmful in patients in lateral decubitus and with the upper lying lungisolatedfromventilation,sinceparalysisofthelower halfofthediaphragmcausestheabdominalorganstoexert greaterpressureupon thedependentlung ---reducing pul-monary complianceand increasing the airway pressures.1
Thisinturnwouldfurtherworsenthelungmechanicsduring thisdelicateperiodofone-lungventilation(OLV).2Although
thereisverylittleinformationontheclinicaleffectofNMRs in chest surgery, more data are available on the use of thesedrugs in situations of low compliance and high air-waypressures,suchasacuterespiratorydistresssyndrome3
or laparoscopic abdominal surgery.4 Improvements in gas
exchange,airwaypressureandlungcompliancehavebeen observedinpatientsadministeredNMRsduringmechanical ventilationincriticalcareunits.
We hypothesize that the absence of muscle tone (diaphragmand chestwall muscles) induced byNMRs will causethegasmixturesupplied bythemechanical ventila-tortofacilitateventilationduringOLVbyimprovingthoracic complianceand/orreducingtheairwaypressures.
Theprimaryobjectiveofourstudywastocompare respi-ratoryfunction(airwaypressureandstaticlungcompliance) according to the degree of patient neuromuscular relax-ation.
Methods
Aprospective, longitudinal observational study wasmade inwhich each patientserved asboth treatedsubjectand control.ThestudywasapprovedbytheEthicsCommittee of Gregorio Mara˜nón University General Hospital (Doctor Esquerdo 46 street, Madrid, Spain) (CEIC 377/13) in Jan-uary2013.Thepatientswereincludedintheprotocolafter signingthecorrespondinginformedconsentdocument.
resectionsurgeryviathoracotomyorvideothoracoscopy,and whorequiredOLVinlateraldecubituswithventilationonly ofthelowerlying(ordependent)lung.Patientspresenting anyofthefollowingcircumstanceswereexcluded:
Seriousheartdiseasewiththeriskofalteredmyocardial compliance(leftventricularejectionfraction<50%,altered diastolicfunction);
Allergyorcontraindicationstotheuseofrocuroniumor sugammadex;
Priorneuromusculardisease; Bodymassindex>30kg·m−2.
Anestheticprotocol
Monitoring initially comprised ECG, peripheral oxygen saturation (SpO2) via pulsioxymetry, noninvasive arterial
pressurerecording,andtheBispectralindex(BIS)®(BIS
mon-itor,Covidien,Minneapolis,USA).
Later,anestheticinductionwascarriedoutwithfentanyl 3---5g·kg−1,propofol2---3mg·kg−1androcuroniumbromide 0.6mg·kg−1(MSD,Oss,TheNetherlands).
After reaching optimum conditions, tracheobronchial intubationwas performed withthe insertion of a double-lumen tube (no. 35---37 in females and 39---41 in males). Correctpositioningwascheckedbyclinical inspectionand fibrobronchoscopy. The patient was then connected to a Primus® ventilator(Dräguer,Lübeck,Germany)for volume controlledmechanicalventilation.Duringtwo-lung ventila-tion,thetidalvolume(Vt)was8mL·kg−1,witharespiratory
frequencyof12rpm,anI/Eratioof1:2,andPEEP5mmHg. DuringOLV,theVtwasreducedto6mL·kg−1,whiletherest
of theparameters remained thesame as duringtwo-lung ventilation.AFiO2allowingSpO2>90%wasused.
A radial artery catheter was placed and a Flo-trac Vigileo®monitor(EdwardsLifesciences,Irvine,CA,USA)was
usedtoobtaindataonStrokeVolumeVariation(SVV), Car-diacIndex(CI)andStrokeVolumeIndex(SVI),amongother parameters.Lastly,thepatientwasplacedinlateral decubi-tusandparavertebralblockipsilateraltotheoperatedside wasperformed(generallyatlevelT5---T6).
Anesthesia was maintained with sevoflurane® (Abbvie, North Chicago, IL, USA) at a concentration of 1%---2% as required to secure adequate depth of anesthesia deter-minedbyBIS40%---60%, andtomaintainthehemodynamic parameters within normal limits. Analgesia was provided in the form of a continuous perfusion of 0.5% bupiva-caine(0.15mL·kg−1
·h−1)throughtheepiduralcatheter,with
100g·kg−1fentanylbolusesifthepatientshowedany clin-icalevidenceofinsufficientanalgesia.
Crystalloid fluid therapy (2mL·kg−1
·h−1) was provided
throughouttheoperation,withoutfastingreplacement.In thecase of a meanblood pressureof <60mmHg,a single 250mL colloid bolus was administered. If the hypoten-sionpersisted,intravenousvasoactivedrugs (ephedrineor phenylephrine)wereprovided.
Neuromuscularrelaxationprotocol
After anesthetic induction but before rocuronium admin-istration,we monitored motor end plate function usinga TOF-WatchSX® acceleromyographicneurostimulator(MSD,
Oss, The Netherlands) fitted onthewrist contralateralto thesurgicalside,torecordtheactivityoftheadductorof thethumb.Initialcalibrationwasmadebefore administer-ing theneuromuscularblockerin ordertoobtain aT1/T4 valueascloseaspossibleto100%andtherebyavoidbiasin assessingfutureresponses.Dependingonthedataobtained with this monitor during the maintenance of anesthesia, neuromuscular block (NMB) was classified into four cate-goriesaccording tothenumber ofresponses after aTrain OfFour(TOF)andthenumberofresponsesafterapplyinga tetaniccurrent(Post-TetanicCount---PTC).
Intense---TOF=0andPTC=0;
DeepNMB(dNMB)---TOF=0andPTC=1; ModerateNMB(mNMB)--- TOF=0---3responses; Recovery---TOF=4withT1/T4>90%.
Once the patient was placed in lateral decubitus, the datacorrespondingtothebaselineconditionwererecorded. The samedatawereagaincollectedonceOLVhadstarted (PRE). More than 30min afterthe start of OLV,we deter-mined whether NMB was moderate or deep. Once the patientpresentedmoderateNMB,weadministeredadoseof 0.3mg·kg−1ofrocuroniumtoinduceintenseordeepNMB,as
registeredbycontinuousmonitoringwiththe neurostimula-tor.Afterreachingthisdegreeofneuromuscularrelaxation, we recordedtheventilatoryandhemodynamic dataevery 5minuntilappearanceofthesecondresponseofthePTC. Specifically, we collected the data obtained after 5 and 15min(POST1andPOST2),andcalculatedthemeanofthe twomeasurements. Duringthethreemeasurementsmade underconditionsofOLV,noneofthemechanicalventilation parametersweremodified.
Thefollowingmechanicalventilatordatawererecorded: airway pressures (peak, plateau, mean and PEEP), static lungcomplianceandpulsioxymetry.Inaddition,werecorded thefollowinghemodynamicparametersateachofthe men-tioned timepoints: heart rate (HR), mean blood pressure (MBP),StrokeVolumeVariation(SVV),CardiacIndex(CI)and StrokeVolumeIndex(SVI).
Allmeasurementsweremadeduringaperiodofatleast 30seconds,withoutsurgeonmanipulationofthe intratho-racicstructures.
Attheendoftheoperation,andafterwashingthe sur-gicalwound andapplyingthedressings, thepatientswere movedto therecovery ward.Hypnosis wasmaintainedto secure BIS<60% beforeadministeringsugammadex. In the supineposition,andafterobtainingtheinformationsupplied bytheTOF-WatchSX®,rocuroniumwasrevertedby adminis-teringasugammadexdoseof4mg·kg−1inthecaseofdNMB
and2mg·kg−1 inthecase ofmNMB.We recordedthetime
elapsedfromsugammadexadministrationtoTOF>90%,and thetimefromclosureofthechestcavitytoextubation.
Statisticalanalysis
Table1 Demographic variablesand respiratory function tests.
n Mean±SD
Weight 76 74±15
Height 76 165±8
Age 76 62.3±15
FEV1pred 76 94±22
FVCpred 76 102±18
FEV1 76 2356±712
FVC 76 3213±804
Weightis expressedas kg. Heightis expressedas cm.Ageis expressedasyears.FEV1andFVCareexpressedasmL.
theMann---WhitneyU-testforsampleswithanon-normal dis-tribution.TheSPSSversion17statisticalpackagewasused throughout.
Results
Seventysixpatientswereincluded
Table 1 describes the demographic characteristics of the patients.Table2shows theevolutionofthehemodynamic parametersduringdeeporintenseNMBcomparedwiththe valuesobtainedduringmoderateNMB.Therewasa signif-icantincrease inHRandasignificantdecreaseinSVV and SVI.
Allpatientsshowedanincreaseinairwaypressuresanda decreaseincompliancewhenOLVwasstarted,accompanied byadropinSpO2(Table3).
Regarding the effect of a 0.3mg·kg−1 rocuronium
dose upon the respiratory mechanics, the mean Ppeak
and Pplateau values were seen to decrease significantly
(from 25.9±5 to 24.8±5 cmH2O and from 23.8±4 to
20.4±5cmH2O,respectively)onprogressingfrommoderate
todeepNMB.Contrarily,meanlungcomplianceincreasedby 2±3mL·cm−1H
2O(POST1)and5.1±3mL·cm−1H2O(POST2)
aftertheadministrationofa0.3mg·kg−1rocuroniumbolus
(Table3),andthemeanSpO2likewisewasseentoincrease.
Allthe patients wereextubated in theoperatingroom (Table 4). At the time of surgical wound closure, no patient presented TOF>90%. Furthermore, 10 patients (13.2%)presented deepNMBat theend of theoperation. After administering sugammadex, all patients presented TOF>90%inalittleovertwoandahalfminutesonaverage. Thetimefromsugammadexadministrationtotherecording ofTOF>90%;thetimefromskinsuturingtoextubation;and theTOF valuesat thetime ofextubation wereall similar amongthepatientswithandwithoutdeepNMBattheend oftheoperation(Table4).
Discussion
DeepNMBduringchestsurgeryinvolvingperiodsofOLVdoes notnegativelyaffectventilationmechanics.Indeed,itmay evenproduceslightimprovementexpressedasadecrease inairwaypressuresandimprovedlungcompliance.
Table2 Hemodynamicvalues.
n Baseline PRE POST1 POST2 Meanoftwomeasurements Mean±SD Mean±SD Mean±SD Mean±SD Mean±SD
HR 76 73±14 77±15 80±14a 79±14a 80±15a
MBP 76 78±15 78±15 76±14 79±13 77±13 CI 76 2.55±0.5 2.89±0.6 2.79±0.5 2.84±0.6 2.8±0.5 SVV 76 11.9±3.8 10.3±5.3 9.5±3.9 9.6±6 9.5±5a
SVI 76 38±11 38±9 37±7 37±8 35±7a
BIS 76 47±8 43±8 43±8 42±7 42±7a
HRisexpressedasbeatsperminute.MBPisexpressedasmmHg.CIisexpressedaslitersperminutepersquaremeterofbodysurface. SVVisexpressedasapercentage.SVIisexpressedasmlperminutepersquaremeterofbodysurface.
a p<0.05oncomparingwiththePREvalues.
Table3 Respiratoryandbloodgasparameters.
n Baseline PRE POST1 POST2 Meanoftwomeasurements Mean±SD Mean±SD Mean±SD Mean±SD Mean±SD
PeakP. 76 19.8±3 25.9±5 24.8±5a 23.8±4a 24.6±5a
PlateauP. 76 17.4±4 21.6±5 20.7±5a 19.6
±4a 20.6
±5a
MeanP. 76 8.5±1 10.4±2 10.2±2a 10.2±2 10.2±2a
PEEP 76 4.8±1 5.5±1 5.5±1 5.6±1 5.5±1 Compliance 76 45.9±11 32.1±11 34.1±11a 37.2±14a 34.2±11a
SpO2 76 99.1±1 94.2±3.1 96.0±3 96.1±2.7a 96.21±3a
End-tidalCO2 76 36±5 36±5 36±5 37±5 36.26±5
Table4 Doseofsugammadexandtimes.
n All mNMB dNMB
Mean±SD Mean±SD Mean±SD
Timesugammadex---TOF90(s) 76 160±64 158±66 163±38
Timeclosure---extubation(min) 76 15.3±7.5 15.1±8 18.2±8
TOFextubation% 76 99±10 99.6±11 97.5±5
Dosesofsugammadexandrocuroniumexpressedasmg.Timeexpressedasseconds.
Classically, the use of neuromuscular relaxants during OLV has been considered risky and even relatively harm-ful. With the patient in lateral decubitus and with the lower lyinglung as the dependent lung, the compressive effectoftheabdominalorgansupontheflacciddiaphragm would cause an increase in intrathoracic pressures, com-plicatingtheventilation of thatlung.1 Inan experimental
study,Bregeonetal.comparedthepulmonaryeffectsin ani-malswithhealthylungssubjectedtomechanicalventilation accordingto whetheror not NMBhadbeen administered. Theauthorsrecordedlesserlungcomplianceandagreater inflammatory response in the animals subjected to NMB, andconcludedthattheeliminationofdiaphragmatic activ-itymightberesponsibleforthedescribedeffects.5In2010,
Xiang et al. reported no benefits in terms of compliance orthesubjectivesurgicaltechnicalconditionswhen admin-isteringrocuroniumincontinuousperfusion orasasimple bolusdose inanestheticinduction among40patients sub-jected togynecological laparoscopic surgery. However,in thegroupadministeredthesingleinductiondose,the sur-gicaltimewassignificantlyshorter---afactthatcouldalter theresultsobtained.4Similarresultshavebeenpublishedby
Paecketal.oncomparingtwogroupsofpatientssubjected topelviclaparoscopicsurgeryandmaintainedwithpropofol andremifentanilinonegroupandaddingrocuroniuminthe other--- nosignificantdifferencesbeingobservedinrelation tothehemodynamicparametersorrespiratorydatasuchas peakpressureor end-tidalCO2.6 However,ourresultsnot
onlyrevealnoworseningofthepeakandplateaupressures and of lung compliance in the patients subjected toOLV underdeepNMB,butactuallysuggestslightimprovementof theseparametersinsuchpatients.Thisallowedtheuseof lowerairwaypressuresformaintainingadequateprotective ventilation,withthebenefitthisimpliesforthepatient.7To
ourknowledge,thisisthefirststudycomparingtheeffectof dNMBversusmNMBuponventilatorymechanicsduringOLV inchestsurgery.
Ontheotherhand,significantdifferenceswereobserved oncomparingthePREandmeanPOSTheartratevalues.The heartratewasseentoincreaseafterdeepblock,possiblyin relationtothepainthatmighthavebeencausedbyinfusion oftheblockerdrug.
Ontheotherhand,asignificantdecreaseinSVVandSVI was recorded on comparing those two timepoints, which could be explained by an increased venous return. The decreaseinventilatorypressuresafterdeepNMBcouldfavor intrathoracicvenous return at thesetimepoints, and thus reducestrokevolumevariability.
One-lung ventilation and NMB are advisable in chest surgery, and specifically in lung resection surgery. During OLV,theuseofNMBwouldfacilitateprotectiveventilation,
whilefailuretodosocouldincreasetheriskofrespiratory complicationsrelatedtoacutelunginjuryduetothedamage which highairwaypressures couldcausein theventilated lung.8,9
One of the scenarios in which the influence of NMB uponventilatorymechanicshasbeenmostextensively inves-tigated is that of patients admitted to critical care due toAcuteRespiratory Distress Syndrome(ARDS). The NMRs mostlyhavebeenshowntofacilitatemechanicalventilation andlessenoxygenconsumption inthesepatients,andcan evenimprovearterialoxygenation.However,theirroutine usedoes have risks(criticalpatientneuropathy) thatmay outweighthepulmonarybenefitsobtained.10Atpresent,this
controversyhascaused NMBtobeadvisedinthefirst48h ofmechanicalventilationandinconcreteandlimited situa-tions---avoidingitsindiscriminateuseoverthesubsequent days.
Foreletal.recordeda lesserinflammatory responsein ventilated patients subjected to NMB than in those who do not receive neuromuscular relaxants.11 Neuromuscular
block therefore should also be considered in this type of surgery, where the perioperative pulmonary proinflam-matoryresponseis associatedtotheappearance ofacute lunginjury---therebyworseningthepostoperativeprognosis ofthepatients.
Classically,there hasbeen concernamonganesthetists overresidualNMB(rNMB)afterextubationandinthe imme-diate postoperative period. The incidence of rNMB varies from 2% to 64%, depending on the literature source,12
though in all cases it complicates patient recovery, with an increased number of complications.13 Sugammadex, a
modified cyclodextrin, acts by binding torocuronium and vecuronium, facilitatingtheir elimination. Comparedwith theuseofneostigmine,itattenuatesthefrequencyofrNMB attheendoftheoperation.14
Limitations
Thedegreeofneuromuscularrelaxationisnotthesameinall muscles,andinthepresentstudywemonitoredrelaxation intheadductorofthethumb,notinthemusclesofthechest cavity(includingthediaphragm).Contractionofthe adduc-torofthethumbhasbeenregardedasthegoldstandardin neuromuscularmonitoring,15 thoughitisknownthatwhen
this muscle is fully paralyzed, the diaphragm and other muscles of the abdominal wall may have recovered from NMB.16 Indeed,the diaphragm isone ofthe muscles most
ofthethumb.17 Allthiscouldexplainwhysome
diaphrag-matic muscle activity may be observed despite adequate NMBasmonitoredatthepatientwrist.18
Besides, pulmonary hipoxic vasoconstriction may alter SpO2,but,weconsidermoresignificativechangesin
compli-anceandinairwaypressuresratherthanisolatedchangein SpO2.
Conclusion
DeepNMBattenuatesthepoorlungmechanicsobserved dur-ingOLVthankstotheinductionofimprovedlungcompliance andlesserairwaypressures.Itthereforecouldberegarded asasimple toolfavoringtheuseof protectiveventilation without complicating early and safe patient extubation, thankstothereversalofNMBwithanadequatesugammadex doseattheendoftheoperation.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
Acknowledgment
To Thoracic Surgery Department without whom this work wouldnothavebeenpossible.
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