Rev. Bras. Anestesiol. vol.67 número1

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REVISTA

BRASILEIRA

DE

ANESTESIOLOGIA

PublicaçãoOficialdaSociedadeBrasileiradeAnestesiologia

www.sba.com.br

SCIENTIFIC

ARTICLE

Effects

of

different

levels

of

end-expiratory

pressure

on

hemodynamic,

respiratory

mechanics

and

systemic

stress

response

during

laparoscopic

cholecystectomy

Oznur

Sen

a,∗

,

Yasemin

Erdogan

Doventas

b

a_Ministery_of_Health_Haseki_Training_and_Research_Hospital,_Department_of_{Anaesthesiology}_and_Reanimation,_Istanbul,_Turkey b_Ministery_of_Health_Haseki_Training_and_Research_Hospital,_Department_of_Biochemistry_Department,_Istanbul,_Turkey

Received9June2015;accepted17August2015 Availableonline12April2016

KEYWORDS PEEP;

Hemodynamic; Respiratory

mechanicsandstress

response

Abstract

Objective:General anesthesia causes reduction of functional residual capacity. And this decreasecan lead toatelectasis andintrapulmonary shuntingin thelung.In this study we wanttoevaluatetheeffectsof5and10cmH2OPEEPlevelsongasexchange,hemodynamic,

respiratorymechanicsandsystemicstressresponseinlaparoscopiccholecystectomy.

Methods:American SocietyofAnesthesiologistI---IIphysicalstatus43 patientsscheduled for laparoscopic cholecystectomywere randomlyselected toreceiveexternalPEEPof5cmH2O

(PEEP5group)or10cmH2OPEEP(PEEP10group)duringpneumoperitoneum.Basal

hemody-namic parameterswere recorded,andarterial bloodgases(ABG) andbloodsampling were doneforcortisol,insulinandglucoselevelestimationstoassessthesystemicstressresponse beforeinductionofanesthesia.Thirtyminutesafterthepneumoperitoneum,therespiratory andhemodynamicparameterswererecordedagainandABGandsamplingforcortisol,insulin, andglucoselevelswererepeated.Lastlyhemodynamicparameterswererecorded;ABGanalysis andsamplingforstressresponselevelsweretakenafter60minutesfromextubation.

Results:There werenostatistical differencesbetween thetwo groupsabouthemodynamic andrespiratoryparametersexceptmeanairwaypressure(Pmean).Pmean,complianceandPaO2;

pHvalueswerehigherin‘PEEP10group’.Also,PaCO2valueswerelowerin‘PEEP10group’.

Nodifferenceswere observedbetween insulinandlacticacidlevelsinthetwo groups.But postoperativecortisollevelwassignificantlylowerin‘PEEP10group’.

Conclusion:Ventilation with 10cmH2O PEEP increases compliance and oxygenation, does

notcausehemodynamicandrespiratory complicationsandreduces thepostoperative stress response.

http://creativecommons.org/licenses/by-nc-nd/4.0/).

∗_{Corresponding}_author.

E-mail:[email protected](O.Sen).

http://dx.doi.org/10.1016/j.bjane.2015.08.015

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PALAVRAS-CHAVE PEEP;

Hemodinâmica;

Mecânicarespiratória

erespostaaoestresse

Efeitosdediferentesníveisdepressãoexpiratóriafinalsobreahemodinâmica, mecânicarespiratóriaerespostasistêmicaaoestressedurantecolecistectomia laparoscópica

Resumo

Objetivo: Aanestesiageralcausaareduc¸ãodacapacidaderesidualfuncionaleessadiminuic¸ão podelevaràatelectasiapulmonareshuntintrapulmonar.Nesteestudopretendemosavaliaros efeitosdeníveisde5e10cmH2Odepressãoexpiratóriafinalpositiva(PEEP)sobreastrocas

gasosas,hemodinâmica,mecânicarespiratóriaerespostaaoestressesistêmicoem colecistec-tomialaparoscópica.

Método: Quarenta e três pacientes, estado físico ASA I-II, agendados para colecistectomia laparoscópica,foramselecionadosaleatoriamenteparareceberPEEPa5cmH2O(grupoPEEP-5)

ouPEEPde10cmH2O(grupoPEEP-10)duranteopneumoperitônio.Osparâmetros

hemodinâmi-cosforamregistrados,gasometriaarterialecoletadesangueforamrealizadasparaestimativa dosníveisdecortisol,insulinaeglicoseparaavaliararespostaaoestressesistêmicoantesda induc¸ãoanestésica.Trintaminutosapósopneumoperitônio,osparâmetroshemodinâmicose respiratóriosforamregistradosnovamenteegasometriaeamostragemparaosníveisdecortisol, insulinaeglicoseforamrepetidos.Eosúltimosparâmetroshemodinâmicosforamregistrados, análiseeamostragemdegasometriapara osníveis derespostaaoestresseforamrealizadas após60minutosdaextubac¸ão.

Resultados: Nãohouvediferenc¸aestatísticaentredoisgruposquantoaosparâmetros hemod-inâmicoserespiratórios,excetopressãomédiadasviasaéreas(Pmédia).OsvaloresdePmédia,

complacência,PaO2edopH forammaioresnogrupoPEEP-10.Tambémosvalores dePaCO2

forammenoresnogrupoPEEP-10.Nãoforamobservadasquaisquerdiferenc¸asentreosníveis deinsulinaedeácidolácticonosdoisgrupos.Porém,oníveldecortisolnopós-operatóriofoi significativamentemenornogrupoPEEP-10.

Conclusão:Ventilac¸ãocomPEEPde10cmH2Oaumentaacomplacênciaeaoxigenac¸ão,não

causa hemodinâmica e complicac¸ões respiratórias e reduz a resposta ao estresse no pós-operatório.

http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction

Generalanesthesiacausesreductionoffunctionalresidual capacity(FRC) due todecreased inspiratory muscletone, increasedabdominalpressureandalteredthoracicvolume.1

Changingtheerectpositiontothesupinepositioncausesa lossofabout20%FRC,andinductionofanesthesiacausesa further loss of 10%.2 _Also, _the _increased_abdominal

pres-sure during laparoscopic procedures results in additional loss of FRC. This decrease in FRCcan lead to atelectasis andformationofintrapulmonaryshuntinginthedepended lungregions.3_{Perioperative}_atelectasis_affects_gas_exchange

andisacceptedasamajorcausefordevelopmentof post-operative hypoxia.4 _Ventilation _with _lower _tidal _volume

andapplicationof positiveend-expiratorypressure(PEEP) improve outcome in acute respiratory distress syndrome (ARDS)andhasbecomearoutinestrategyforthetreatment ofthepatientwithARDS.5_However,_recent _{meta-analyses}

have sustained that ventilation during general anesthesia withlowertidalvolumesandPEEPcanalsobenefitpatients without ARDS.6 _Also,_application _of _PEEP _has _been _shown

tobeeffectiveinpreventingatelectasisduringanesthesia. PEEP is a frequentlyemployed strategyin anesthesiology, but it has capacity to harm as well as to yield benefi-cialoutcomes.7 _Depending _on _the _PEEP _level, _a _decrease

in cardiac output (CO) can be induced through increased

intrathoracicpressure(ITP)andreducedventricularpreload andsystemicvenousreturnpressuregradient.8

This study was undertaken to evaluate the effects of different PEEP levels on gas exchange, hemodynamics and stress response in the settings of increased intra-abdominalpressure(IAP)createdbyCO2pneumoperitoneum

forlaparoscopiccholecystectomy.

Methods

Thisprospectiverandomizedstudywasconductedwiththe approval of the institute’s research and ethics commit-teeandafterobtaining writteninformedconsentfrom43 patients, aged 18---65 years and of American Society of Anesthesiologist (ASA) I---II physical status, scheduled for laparoscopiccholecystectomy.Patientswithmorbidobesity (BMImorethan 30kgm−2₎_or _history_of _diabetes _mellitus,

endocrine,respiratory,cardiopulmonaryand cerebrovascu-lardiseases were excluded fromthestudy.Also,only the casesadmittedtothetheateruntil11:00A.M.wereincluded inthisstudy.Thepatientswererandomlyselected,by open-ing sealed envelopes, to receive either external PEEP of 5cmH2O(PEEP5group,n=20)orexternalPEEPof10cmH2O

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In the operating theater, baseline electrocardiogram (ECG), heart rate (HR), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP),hemoglobinoxygen saturation(SpO2)andend-tidal

carbon dioxide (ETCO2) were recorded using a

multipa-rametermonitor. Baselinearterialbloodgases(ABG)were measuredandbloodsamplingwasdoneforcortisol,insulin andglucoselevelestimationstoassess thesystemicstress response. Anesthesia was induced by 2mgkg−1 _propofol,

2␮gkg−1 fentanyl citrate, and 0.6mgkg−1 rocuronium

bromide. Anesthesia was maintained with 1.0 MAC of sevoflurane in a mixture of 50% oxygen and air and the ventilator was set with8mLkg−1 _tidal _volume_calculated

using the predicted body weight and 12min respiratory rate with an I:E ratio of 1:2 at fresh gas flow 1Lmin−1_.

The ‘PEEP5group’received5cmH2O PEEP,andthe‘PEEP

10 group’ received 10cmH2O PEEP level. Before

pneu-moperitoneum, HR, MAP, ETCO2, Ppeak, Pplato, and Pmean

were recorded. Pneumoperitoneum was created by CO2

insufflationandIAPwassettobemaintainedat14mmHg−1

bymeans ofanautomaticinsufflator.Thirtyminutesafter thepneumoperitoneum, therespiratoryandhemodynamic parameterswererecordedagainandABGandsamplingfor cortisol,insulin, glucoselevelswere repeated.Anesthesia was maintained until the end of surgery, neuromuscular blockade wasantagonizedwithsugammadexand tracheal extubation was carried out when the patient was fully awake. Recording of hemodynamic parameters and ABG, and sampling for cortisol, insulin, glucose levels were repeatedforthelasttimeat60minafterextubation.

Table1 Beforeandduringthepneumoperitoneumtime.

Group

PEEP5 PEEP10

n % n %

Gender

Men 8 40.0 6 26.1 0.331

Women 12 60.0 17 73.9

Mean±SD Median Mean±SD Median p

Age(years) 49.0±13.5 49 43.5±12.6 41.5 0.180

Weight(kg) 75.1±11.4 80 72.3±10.6 71 0.416

Heartrate

1 75.6±5.9 76 83.3±11.5 80 0.090

2 81.9±12.2 84 77.7±15.5 74 0.471

3 84.0 84 78.9±15.0 78.5

---SAP

1 131.9±17.1 134 131.2±23.9 128.5 0.941

2 119.2±26.3 119 126.4±14.6 120 0.467

3 142.0 142 119.8±13.4 118.5

---DAP

1 82.3±15.1 84.5 84.8±11.7 83 0.651

2 75.4±16.0 79 84.7±8.3 82 0.134

3 89 89 73.3±8.7 73

---MAP

1 103.9±13.3 101.5 108.9±15.4 105 0.391

2 96.6±19.3 99 103.3±10.5 103 0.352

3 115 115 90.3±8.2 90

---Ppeak

1 20.7±5.9 18.5 20.6±2.8 20 0.961

2 23.3±3.8 22.5 25.1±2.1 25 0.053

Pplato

1 18.8±4.2 17.5 18.0±5.1 19 0.745

2 21.4±3.7 20.5 23.2±2.1 22 0.054

Pmean

1 9.5±1.4 9 12.4±1.3 13 0.005

2 10.2±1.1 10 13.7±1.3 14 <0.001

Compliance

1 41.0±10.4 40 60.4±13.1 58 0.009

2 34.7±6.7 34.5 41.4±5.9 41 0.001

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Statisticalanalysis

WindowsprogramSPSS15.0wasusedforthestatistical

anal-ysisoftheresults.Descriptivestatisticsweregiveninterms

ofnumbersandpercentagesfor categoricalvariables,and

interms of themean, standarddeviation andthemedian

for the numerical variables. Comparison of two

indepen-dentgroupsofvariableswascarriedoutusingtheStudent

ttestwhenmeetingthenormaldistributioncriteria,orby

theMann---WhitneyUtestwhenthesecriteriawerenotmet.

Relationship betweennumericalvariableswasassessedby

meansoftheSpearmanCorrelationAnalysis.Thedifferences

betweencategorical variableswere evaluatedbythe

Chi-squareanalysis.Statistical ˛(alpha)significancelevelwas

acceptedwiththep-valuebelow0.05.

Results

Physicalcharacteristicsanddemographicparametersofthe

twopatient groups were closely comparable. Also, there

werenostatisticallysignificantdifferencesbetweenthetwo

groupswithrespecttothehemodynamic parameters(HR,

SAP,DAP,andMAP)andtherespiratoryparametersofPpeak

andPplato levels.Butthemeanairwaypressure(Pmean)and

compliancelevelswerestatisticallyhigherinPEEP10group

beforeandduringthepneumoperitoneumtime(Table1).

The meanETCO2 levelsweresamefor thetwogroups.

Althoughnodifferenceswereobservedin thePaO2values

betweenthetwogroupspreoperativelyandinthe postop-erativeperiod,thevalueswerehigherinthe‘PEEP10group’ overthe durationof pneumoperitoneum(Table 2,Fig.1). Beforepneumoperitoneum and during pneumoperitoneum

Table2 Overthedurationofpneumoperitoneum.

Group p

PEEP5 PEEP10

Mean±SD Median Mean±SD Median

ETCO2

1 31.5±4.9 31.5 33.2±2.4 33 0.428

2 33.0±4.2 33 34.8±3.5 34 0.526

PaO2

---1 85.0±15.7 80 91.9±14.4 93 0.158

2 135.2±36.9 132 176.1±37.9 172 0.001

3 96.4±22.8 88.5 91.5±12.2 90 0.838

PCO2

1 38.5±4.6 39 36.5±4.3 36 0.165

2 41.9±5.5 40 35.9±5.5 35 0.001

3 39.6±4.9 40 35.0±5.2 34.5 0.006

pH

1 7.40±0.05 7.41 7.40±0.05 7.40 0.650

2 7.35±0.05 7.35 7.39±0.05 7.38 0.008

3 7.37±0.04 7.37 7.41±0.08 7.41 0.081

SpO2

1 100 100 98.0±1.1 98

---2 99 99 99 99

---Cortisol

---1 13.1±5.8 12.9 12.1±5.7 12.0 0.573

2 23.4±6.2 22.1 20.5±5.5 21.6 0.115

3 28.3±6.0 26.1 17.3±11.1 15.9 <0.001

˙Insuline

1 4.6±3.3 5.1 4.5±3.0 4.1 0.880

2 3.8±4.5 2.5 3.4±2.9 2.6 0.830

3 7.4±5.7 6.1 9.1±9.7 5.5 0.980

Glucose

1 77.5±13.7 77.0 88.1±12.7 89.0 0.012

2 100.3±18.7 98.0 113.7±24.7 110.0 0.088

3 108.8±20.3 102.5 109.0±32.5 98.0 0.342

Laktat

1 2.8±0.8 2.9 2.2±0.8 2.3 0.206

2 2.9±0.2 3.0 2.6±0.8 2.8 0.351

3 2.5±0.7 2.6 1.5±0.9 1.6 0.084

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200

180

160

140

120

100

PEEP5 Pa02 1 Pa02 2 Pa02 3

Mean - 95, % CI

PEEP10 80

Figure1 ChangesinPaO2levels(PaO21,preoperativetime;

PaO22,peroperativetime;PaO23,postoperativetime).

time,PaCO2valueswerelowerin‘PEEP10group’(Table1,

Fig.2).MeanpHvaluesofthe‘PEEP10group’werehigher thanthoseofthe‘PEEP5group’(p<0.01)(Table2,Fig.3). Postoperativemeancortisollevelofthe‘PEEP10group’was significantlylowerthanthat oftheothergroup(p<0.001) (Table2,Fig.4).Nodifferenceswereobservedbetweenthe insulinandlacticacidlevelsthetwogroups.Preoperative glucoselevelofthe‘PEEP10group’washigherthanthatof the‘PEEP5group’(p<0.05)(Table2,Fig.5).

44

42

40

38

36

34

32

PEEP5

Mean - 95, % CI

PC02 1 PC02 2 PC02 3

PEEP10

Figure 2 Changes in PaCO2 levels (PaCO2 1, preoperative time; PaCO2 2, peroperative time; PaCO2 3, postoperative time).

7450

7425

7357

7350

7325 7400

PEEP5

Mean - 95, % CI

PH 1 PH 2 PH 3

PEEP10

Figure3 ChangesinpHlevels(pH1,preoperativetime;pH 2,peroperativetime;pH3,postoperativetime).

Discussion

This studyaimedtodemonstrate theeffectsof the appli-cation of 5cmH2O PEEP versus 10cmH2O PEEP during

pneumoperitoneum in laparoscopic abdominal surgery on any improvement on oxygenation and compliance, pre-vention of atelectasis and the differences in changes in therespiratory,hemodynamicparametersandthesystemic stressresponse.

Recent reports have demonstrated that application of PEEPduringgeneralanesthesia,especiallyforlaparoscopic surgery,improvescomplianceandoxygenation.9_In_a_study

30

25

20

15

10

PEEP5

Mean - 95, % CI

Cortizol 1 Cortizol 2 Cortizol 3

PEEP10

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130

Glucose 1 Glucose 2 Glucose 3

PEEP5

Mean - 95, % CI

PEEP10 120

110

100

90

80

70

Figure5 Changesinglucoselevels(Glucose1,preoperative time;Glucose2,peroperativetime;Glucose3,postoperative timevalues).

to evaluate the effect on cerebral oxygen saturation of 0cmH2O PEEP and of 10cmH2O PEEP application during

laparoscopic cholecystectomy, Hyun etal.concluded that 10cmH2OPEEPusagesavedcerebraloxygensaturation

with-outadverse effectsonhemodynamicstability.10 _In_another

study,employing14,8and14mmHg−1_IAP_pressure,

respec-tively, on groups given 0, 5 and 10cmH2O PEEP, they

observedthatapplicationofPEEPatthecorrespondingIAP helped maintain CO2 elimination and improved

oxygena-tionwithouthemodynamicdisturbance.11_Furthermore,_the

reviewbytheCochraneCollaborationgroupon postopera-tivemortalityandpulmonarycomplicationswithand with-out useof PEEP has suggested, albeitinconclusively, that PEEPimprovespostoperativeatelectasisandoxygenation.12

On the other hand, the PROVHILO trial with 900 cases of open abdominal surgery under general anesthe-sia with 8mLkg−1 _tidal _volume _and _recruitment, _using

either 2cmH2O PEEP or 12cmH2O PEEP, did not

demon-stratesignificantdifferencesbetweenthetwogroupswith respecttopostoperative pulmonary complicationsdespite thehigherpreoperativeoxygenationvaluesinthe12cmH2O

PEEP group, and the greater need of oxygenation by the 2cmH2O PEEP group. They concluded that elevated PEEP

andrecruitment maneuver in open abdominalsurgery did not protect against pulmonary complications and mortal-ity,anddefendedtheventilationstrategywithoutlowtidal volume,lowlevelPEEPandrecruitment.13

Whenlevelsof0,5,10and15cmH2OPEEPwereapplied

in cardiacsurgery, it wasreportedthat asthePEEP level wasincreased,respiratorysystemtotalresistanceand elas-ticrecoilweredecreased;oxygenationandCO2elimination

increased;deadspaceandshuntingweredecreased;arterial oxygencontent,oxygenconsumptionandtheoxygen extrac-tionratewereincreaseddespitetheprogressivereduction inthecardiacindex;andnodifferencesinthemean

arte-rialbloodpressurewasdemonstrablebetweenthedifferent PEEPgroups.Itwasconcludedthatalthoughapplicationof PEEPabovethe10cmH2OPEEPlevelincreasedoxygenation,

itshouldbe cautiouslyappliedespeciallyin patients with marginalcardiacfunctionduetocontractilitydisturbances orhypovolemia.14_Daniel_et_al.,_after_evaluating_the_effects

of5,8and10cmH2OPEEPapplicationsonthedurationof

mechanicalventilation aftercoronaryarterybypass graft-ing surgery, reported a significantly shortened ventilation timeinthe10cmH2OPEEPgroup.15Karstenetal.evaluated

regional ventilation using electrical impedance tomogra-phyon32patientsundergoinglaparoscopiccholecystectomy eitherwith0(zero)cmH2OPEEP (theZEEPapplication) or

10cmH2O PEEP. They reported that recruitment

maneu-verand10cmH2OPEEPapplicationinlaparoscopicsurgery

improvedoxygenationandcorrectedcompliance.9_The_same

group of authors investigated the effects of 0, 3, 5, 7 and10cmH2OPEEPapplicationduringrobot-assisted

laparo-scopic radical prostate surgery on the hemodynamic and respiratoryparameters.TheyreportedthatHRandMAP val-ues did notvary with the PEEP level, but the PaO2 level

wassignificantlylowintheZEEPgroupofpatientsandmost elevated inthe 10cmH2O PEEP group. Onepatientin the

10PEEPgrouphadsubcutaneousemphysemaresolvedafter cessationoftheinsufflation.Theyconcludedthat applica-tion of 7cmH2O PEEP resulted in significant oxygenation

augmentation without excessive peak airway pressure or depression of hemodynamic parameters during prolonged laparoscopicsurgery.16

Inourstudy,we observedthat duringthe pneumoperi-toneum period, PaO2, compliance, Pmean, and pH levels

werehigher in the 10cmH2O PEEP group as compared to

the5cmH2OPEEPgroup.Although5cmH2OPEEPpreserved

oxygenationduringpneumoperitoneum,10cmH2OPEEP

pro-duced a significant improvement in oxygenation. Similar observations were made by Andrea et al. during laparo-scopic gynecological surgery. PEEP application resulted in recruitmentinthealveoli,improvingcardiacandpulmonary functions and thereby improving oxygenation, enhancing CO2washoutandinhibitionofthevasoconstrictorreflex.

It was argued that while 5cmH2O of PEEP acted as a

shieldagainstthenegativecardiopulmonaryeffectsinduced bypneumoperitoneum,10cmH2OofPEEPactuallyimproved

the effects.17 _Although _the _most _common _{complications}

of high PEEP application are observed in the hemody-namicparameters, especiallyin hypovolemic patients, on including respiratory effects such as barotrauma, we did notencounterhemodynamicorrespiratorycomplicationsin ourseriesofpatients. Inpatientsundergoinglaparoscopic inguinal hernia surgerywithapplication of 8mLkg−1 _tidal

volumewith0,5 and10cmH2O PEEP,end-expiratory lung

volume(EELV),measuredwiththenitrogen wash-out/wash-in method using electrical impedance tomography, was increasedduringapplication of10cmH2OPEEP whichalso

homogenizedventilationdistribution.18

We observed, when evaluating the effects of 5 and 10cmH2OPEEPapplicationonthesystemicstressresponse,

that preoperative blood glucose levels, although signifi-cantlyelevated,werestillwithinthephysiologicallimitsin the10cmH2OPEEP group,while thecortisollevelwas

(7)

couldnotfindanotherstudyintheliteratureontheeffects ofPEEPlevelonthesystemicstressresponseparametersto beabletomakedirectcomparisonsontheresults.

However, in studies evaluating the inflammatory response, it was found out that PEEP was beneficial at high inspiratory pressure and caused some stress, but imposedonlymoderatestressatlowinspiratorypressure.19

Weingartenetal.comparedtheeffectsof‘lowtidalvolume withhigh (12cmH2O) PEEP’ application versus ‘high tidal

volume with ZEEP (0cmH2O PEEP) application’ on the

systemicinflammatory responseparametersIL-6and IL-8, andfoundnodifferencesbetweenthetwogroups.Butthe perioperative oxygenation of the ‘low tidal volume and 12cmH2O PEEP’ group wasincreased and lung mechanics

were muchbetter.20 _In _our _study,_the _observation _of _low

postoperativecortisol levelswith10cmH2O PEEP

applica-tionmayberelatedtobetterperoperativeoxygenationand compliance.

Conclusion

We believe that during laparoscopic cholecystectomy surgery,ventilation with10cmH2OPEEP increases

compli-ance and oxygenation does not cause hemodynamic and respiratory complications and reduces the postoperative stressresponsewiththisstudy.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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