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Perioperative management of adult diabetic patients.
Intraoperative period
Gaelle Cheisson, Sophie Jacqueminet, Emmanuel Cosson, Carole Ichai,
Anne-Marie Leguerrier, Bogdan Nicolescu-Catargi, Alexandre Ouattara, Igor
Tauveron, Paul Valensi, Dan Benhamou
To cite this version:
Gaelle Cheisson, Sophie Jacqueminet, Emmanuel Cosson, Carole Ichai, Anne-Marie Leguerrier,
et al..
Perioperative management of adult diabetic patients.
Intraoperative period.
Anaes-thesia Critical Care & Pain Medicine, Elsevier Masson, 2018, 37 (Supplement 1), pp.S21-S25.
�10.1016/j.accpm.2018.02.018�. �hal-02626515�
Guidelines
Perioperative
management
of
adult
diabetic
patients.
Intraoperative
period
Gae¨lle
Cheisson
a,
Sophie
Jacqueminet
b,
Emmanuel
Cosson
c,d,
Carole
Ichai
e,f,
Anne-Marie
Leguerrier
g,
Bogdan
Nicolescu-Catargi
h,
Alexandre
Ouattara
i,j,
Igor
Tauveron
k,l,m,n,
Paul
Valensi
c,
Dan
Benhamou
a,*
,
working
party
approved
by
the
French
Society
of
Anaesthesia
and
Intensive
Care
Medicine
(SFAR),
the
French
Society
for
the
study
of
Diabetes
(SFD)
a,*
a
Departmentofsurgicalanaesthesiaandintensivecare,SouthParisuniversityhospital,hoˆpitaldeBiceˆtre,AP–HP,78,rueduGe´ne´ral-Leclerc,94275Le Kremlin-Biceˆtre,France
b
Instituteofcardiometabolismandnutrition,Departmentofdiabetesandmetabolicdiseases,hoˆpitaldelaPitie´-Salpeˆtrie`re,AP–HP,75013Paris,France
c
Departmentofendocrinology,diabetologyandnutrition,hoˆpitalJean-Verdier(AP–HP),Paris13university,SorbonneParisCite´,CRNH-IdF,CINFO, 93140Bondy,France
dUMRU1153Inserm,U1125Inra,CNAM,SorbonneParisCite´,Paris13university,93000Bobigny,France e
Departmentofversatileintensivecare,hoˆpitalPasteur2,CHUdeNice,30,voieRomaine,06001Nicecedex1,France
f
InsermU1081,CNRSUMR7284(IRCAN),UniversityHospitalofNice,06001Nice,France
g
Departmentofdiabetologyandendocrinology,CHUdeRennes,hoˆpitalSuduniversityhospital,16,boulevarddeBulgarie,35056Rennes,France
h
Departmentofendocrinologyadmetabolicdiseases,hoˆpitalSaint-Andre´,Bordeauxuniversityhospital,1,rueJean-Burguet,33000Bordeaux,France
i
Bordeauxuniversityhospital,DepartmentofAnaesthesiaandCriticalCareII,MagellanMedico-SurgicalCentre,33000Bordeaux,France
jInserm,UMR1034,BiologyofCardiovascularDiseases,universite´ deBordeaux,33600Pessac,France
kDepartmentofendocrinologyanddiabetology,ClermontFerranduniversityhospital,58,rueMontalembert,63000Clermont-Ferrand,France l
UFRme´decine,ClermontAuvergneuniversity,,28,placeHenri-Dunant,63000Clermont-Ferrand,France
m
UMRCNRS6293,InsermU1103,GeneticReproductionanddevelopment,Clermont-Auvergneuniversity,63170Aubie`re,France
n
Endocrinology-Diabetology,CHUG.-Montpied,BP69,63003Clermont-Ferrand,France
Perioperativehyperglycaemiaisassociatedwithanincreasein morbidityandmortalityindiabeticandnon-diabeticpatients.It
results in delayed healing and an increase in the frequency of infections.Correctionofhyperglycaemiaimprovestheprognosisof thesepatientsandobjectivesforthebestbenefit/riskratioshould bedetermined.
ARTICLE INFO Articlehistory:
Availableonline16March2018 Keywords: Diabetes Perioperative Insulintherapy Insulinpump Glycaemiccontrol Insulinresistance ABSTRACT
Perioperative hyperglycaemia (>1.80g/L or 10mmol/L) increases morbidity (particularly due to infection)andmortality.Hypoglycaemiacanbemanagedintheperioperativeperiodbydecreasing bloodsugarlevelswithinsulinbetween0.90and1.80g/Lbutitmayoccurmorefrequentlywhenthe goalisstrictnormoglycaemia.Weproposecontinuousadministrationofinsulintherapyviaanelectronic syringe(IVES)intype-1diabetes(T1D)andtype-2diabetes(T2D)patientsifrequiredorincasesofstress hyperglycaemia.StoppingapersonalinsulinpumprequiresimmediatefollowonwithIVESinsulin.We recommend 4mg dexamethasonefor theprophylaxis of nausea and vomiting, rather than 8mg, combinedwithanotherantiemeticdrug.Theuseofregionalanaesthesia(RA),whenpossible,allowsfor bettercontrolofpostoperativepainandshouldbeprioritised.Analgesicrequirementsarehigherin patientswithpoorlycontrolledbloodsugarlevelsthaninthosewithHbA1c<6.5%.Thestruggleto preventhypothermia,theuseofRAandmultimodalanalgesia(whichallowforamorerapidrecoveryof bowelmovements),limitationofbloodloss,earlyambulationandminimallyinvasivesurgeryarethe preferredmeasurestoregulateperioperativeinsulinresistance.Finally,diabetesdoesnotchangethe usualrulesoffastingorofantibioticprophylaxis.
C 2018TheAuthor.PublishedbyElsevierMassonSASonbehalfofSocie´te´ franc¸aised’anesthe´sieetde
re´animation(Sfar).ThisisanopenaccessarticleundertheCCBYlicense(http://creativecommons.org/ licenses/by/4.0/).
* Correspondingauthor.
E-mailaddress:dan.benhamou@aphp.fr(D.Benhamou).
https://doi.org/10.1016/j.accpm.2018.02.018
2352-5568/ C2018TheAuthor.PublishedbyElsevierMassonSASonbehalfofSocie´te´ franc¸aised’anesthe´sieetdere´animation(Sfar).Thisisanopenaccessarticleunderthe
1. Consequencesofperioperativehyperglycaemia 1.1. Transversaldata
Most studies in this area have been conducted in cardiac surgery or intensive care units (ICUs). A significant positive relationhasbeenfoundbetweenmaximal perioperative hyper-glycaemiaandperioperativemortality[1],aswellasa10-times higher risk of complications when postoperative glycaemia was>2.5g/L (13.5mmol/L) [2]. In a retrospective study in 409 patients (20% diabetics), Gandhi et al. [3] concluded that perioperativehyperglycaemiawasanindependentriskfactorfor perioperativecomplicationsincludingmortalityandinfectionand thatanincreaseinglycaemiaof0.2g/L(1.1mmol/L)above1g/L (5.5mmol/L)increasedtheriskofpostoperativecomplicationsby 34%. Ouattara et al. found that in 200 diabetic patients who underwentcardiacsurgery,uncontrolledperioperative hypergly-caemia(>2g/Lor11mmol/L)wasassociatedwitha7-foldhigher riskofpostoperativecomplications[4].Innon-cardiacsurgery,a prospectivestudycomprising20%diabeticpatientsalsofoundthis link[5].
Perioperativehyperglycaemiaisanindependentriskfactorfor postoperativemorbidity/mortality[1,6].Inpatientswith undiag-noseddiabetes,hyperglycaemiawasassociatedwithanincreased risk of infection, re-interventions and intra-hospital mortality
[7,8].
In particular, a correlation exists between perioperative hyperglycaemia and the frequency of infections in diabetic patients.Incardiacsurgery,thereisanincreasein sternalbone infections in patients with mean preoperative blood sugar levels>2g/L(11mmol/L)[9].ForZerretal.,patientsdeveloping postoperativemediastinitis presented mean blood sugar levels thatweresignificantlyhigherduringthe48hpost-surgery(2.1vs 1.9g/L,P<0.003)(11.4vs10.5mmol/L)[8].
The prognosis of hyperglycaemia appears to be different depending on whether it is stress hyperglycaemia or chronic imbalanceinapatientwithpre-existingdiabetes.Inacohortof patients undergoing non-cardiac surgery, Krinsley et al. [10]
reporteda differentglycaemiathresholdabovewhichmortality wassignificantlyincreased,whetherthepatientwasdiabetic(i.e. 1.8g/L or 10mmol/L) or not (i.e. 1.4g/L or 7.8mmol/L). Many studieshavereportedthatperioperativestresshyperglycaemia,at asamelevelofglycaemia,waspotentiallylessharmfultoapatient whowaspreviouslyknowntobediabetic[7,11].
Theprognosticimpactofperioperativehyperglycaemia justi-fiesits earlydetectionby performingregular measurementsof bloodsugarlevels,anditscorrection,particularlyinat-risksurgical patients (age>60-years, existence of a metabolic syndrome, previous history of transitory hyperglycaemia, cardiovascular history)[12].
1.2. Glycaemicobjectives:observationalstudies
Furnaryetal.[6]showedin4051aortocoronarybypasspatients studied between 1987 and 2001 that the management of hyperglycaemiaintheperioperativeperiodofthe26%ofpatients withdiabetesdecreasedthemortalitytoalevelcomparabletothat of non-diabetic patients. The management of hyperglycaemia evolved duringthestudy frommanagement thatwas uniquely postoperativethen perioperative, to perioperative until 3 days post-surgery,includingcontinuousadministrationofinsulinwith regularly reduced glycaemic objectives (1.5–2g/L or 8.25– 11mmol/L,then1–1.50g/Lor5.5–8.25mmol/L).Themeanblood sugar levels decreased to 1.77g/L (9.73mmol/L) compared to 2.14g/L (11.8mmol/L) inthehistoric group.Themortality rate decreasedby36% comparedtotheexpectedvalue,and by57%
comparedtothehistoricgroup(2.4vs.4.0%),reachingthatof non-diabetics(whichremainedstableduringthestudy).Thedecrease inmortalityincludedmortalityofcardiacoriginandacorrelation wasshownbetweenthedegreeofhyperglycaemiaandmortality. Comparableresultswerefoundinretrospectivestudieswherethe incidenceofmediastinitisandmortalitywasdecreasedby37%and 29%,respectively,ingroupswithaglycaemicobjectiveof<2g/L (11mmol/L) [8,13]. In a retrospective case-control study, D’Alessandro et al. [14]concluded that control of blood sugar levelsbetween1.5and2g/L(8.25to11mmol/L)isbeneficial,but onlyinpatientswithaEUROSCORE>4.
Aninitialmeta-analysisstudyin2004reporteda15%decrease in mortality in ICU when glycaemia wascontrolled by insulin therapy [15]. In diabeticpatients in theperioperativeperiod,a reduction of blood sugar levels to <1.8–2g/L (10–11mmol/L) decreased morbidity, in particular bone infections, duration of hospital stay and mortality of cardiac origin, particularly in patientswithbloodsugarlevels>1.75g/L(9.6mmol/L)[6].
Studies comparing different blood sugar levels in surgery regarding strictvs. moderate control,suchas theretrospective studyof4658diabeticpatientsbyBhamidipatietal.demonstrated thatpatientswithbloodsugarlevelsbetween1.26g/Land1.79g/L (7–10mmol/L) had a better prognosis than patients with levels<1.26g/L (7mmol/L) during aortocoronary bypass
[16]. Similarly, moderate control of glycaemia (<1.8g/L or 10mmol/L) decreased the number of hypoglycaemic episodes comparedtostrictcontrol(0.8–1.2g/Lor4.4–6.6mmol/L)without anydifferencesinmorbidity/mortalityincardiacsurgery[17,18]. 1.3. Glycaemicobjectives:randomisedinterventionalstudies
In a randomised study, Lazar et al. reported a significant decreaseinmorbiditywhencomparinginfectionsatthecardiac operative site (0% vs. 13%, P<0.01), in the treated group (glycaemic objective between 1.2 and 1.8g/L or 6.6 and 10mmol/L) compared to the untreated group (glycaemic objective<2.50g/Lor13.7mmol/L).Themeanbloodsugarlevels of the two groups were 1.38g/L (7.6mmol/L) and 2.26g/L (12.4mmol/L), respectively [19]. Tight perioperative glycaemic controlstartedbeforeinductionofanaesthesiaandcontinueduntil the twelfth hour post-surgery (1.26–2.00g/L or 7–11mmol/L), improved perioperative haemodynamic control. Follow-up five yearslaterdemonstratedabeneficialeffectonlong-termmortality
[19].
The studies mentioned above have determined the upper limitfortheglycaemicobjective,butdoesnormoglycaemiacarry a supplementary benefit? In 2001, van den Berghe et al. publishedthefirstrandomisedstudy(1558patientsinsurgical ICUs;60%incardiacsurgery,13%diabeticpatients)tocompare the strict objective (0.8–1g/L or 4.4–5.5mmol/L) versus the conventional objective (1.8–2g/L or 10–11mmol/L), demon-stratingadecreaseinmortalityof8%andadecreaseinmorbidity (including septicaemia and duration of antibiotic therapy)
[20]. van den Berghe et al. conducted a second study in a medicalICU(samerandomisationmodel,sameobjective)butdid notfindanybenefitofintensivetreatmentuponmortalityand septicaemia. The mortality decreased only in patients with a hospital stay>3 days, except for diabetics who represented approximately17%ofthepopulation.Intermsofmorbidity,they noted a decrease in the rate of renal failure, much earlier withdrawalofventilation,ashorterstayintheICUandearlier dischargefromhospital[21].
The VISEP study [22] in septic shock, and the Glucontrol study [23] in ICUs were stopped early due to more frequent severe hypoglycaemias in the group receiving intensive treat-ment. The NICE-SUGAR [24] multicentre, randomised study
G.Cheissonetal./AnaesthCritCarePainMed37(2018)S21–S25 S22
carriedouton6104patientsinsurgicalandmedicalICUs(20% diabeticpatients), comparing twoglycaemic objectives: 0.81– 1.08g/L(4.4–6mmol/L)vs. 1.8g/L(10mmol/L),showed the absenceofbenefitintermsofmorbidity. Incontrast,mortality was increased (+2.8%) as well as the number of severe hypoglycaemias in the group receiving intensive treatment. Themean bloodsugarlevelsobtainedin thetwogroupswere 1.15g/L (6.3mmol/L) vs. 1.44g/L (8mmol/L), respectively. In 2008, a meta-analysis [25] of the largest randomised studies concluded not only that there was no benefit of intensive managementinICUsbutalsothattherewasanincreasedriskof hypoglycaemia.
Itshouldbepointedoutthatinthemostrecentrandomised studies(NICE-SUGARinparticular),thegroupreceiving conven-tionaltreatmenthadmeanbloodsugarlevelsthatwereclearlyless than2g/L(11mmol/L).Intensivetreatmentwasnotsuperiorto conventional treatment but enabled blood sugar levels to be maintainedat<1.8g/L(10mmol/L),atthelevelsobtainedduring establishmentoftheprotocolinolderstudiesthatdemonstrateda benefitonmorbidity/mortality.
Finally, in a randomised study of 300 patients undergoing aortocoronarybypass, Umperriezetal. [26]compared different glycaemic objectives including strict control (1.1–1.4g/L or 6– 7.7mmol/L)andmoderatecontrol(1.4–1.8g/Lor7.7–10mmol/L) ofglycaemia.Nodifferencesinmorbidity,sternalinfectionrate, mortalityand duration of hospital staywere found, but hypo-glycaemic episodeswere morefrequent in the groupreceiving intensivetreatment.
1.4. Overall,whatglycaemicobjectivesareproposed?
Hyperglycaemia(>1.80g/Lor10mmol/L)inthe periopera-tive period increases morbidity (in particular infections) and mortality. The control of glycaemia should start in the preoperativeperiod and be continuedinthe early days after theoperation. Patients benefit from a reductioninglycaemia rather than intense insulin therapy and the objective of normoglycaemia (0.80–1.20g/L or 4.4–6.7mmol/L) increases the rate of severe hypoglycaemia and possibly mortality. Moderate glycaemic control (1.40–1.8g/L or 7.7–10mmol/L) appears,tobethebestcompromiseresultinginadecreasein morbidity/mortalitywithoutincreasingthefrequencyof hypo-glycaemia.
Maintainingstablebloodsugarlevelsbetween1.40and1.80g/L (7.7–10mmol/L)requirescomplexprotocolsemployingIVinsulin andthesearedifficulttoexecute,intheabsenceofa computer programme.
A broaderobjective is desirable:glycaemic control between 0.90and1.80g/L(5–10mmol/L),acut-offleadingtotherapeutic adjustment,toavoidhypoglycaemiaand tomaintainglycaemia below1.80g/L(10mmol/L).
(PracticalsheetsG,H,J,K,L,O).
2. Perioperativemanagementofglycaemia 2.1. Generalprinciples(PracticalSheetsO,G,H,J,K)
Inthepreoperativeperiod,werecommendthatmanagementof diabeticpatientsbebasedonthefollowingprinciples[27–30]: avoid prolonged fasting: schedule the diabetic patient for
surgeryasearlyaspossibleinthemorning;
haveaglycaemicobjectiveof5–10mmol/L(0.9–1.8g/L).There is no consensuson theoptimum glycaemia threshold in the perioperativeperiod,butatargetbloodsugarlevelof<1.8g/L (10mmol/L)willhelptoavoidhypoglycaemia[31–35];
ifinsulin is required: ultra-rapidshort-acting analogues are preferred,administeredcontinually,byIVES[36–38];always giveninassociationwithIVglucose(equivalentof4g/h)and electrolytesdependingontherequirementsandbeingcareful to avoid hypokalaemia induced by insulin. There is great variabilitydependingontheprotocolsusedpreoperativelyfor insulintherapy,withoutanyevidencethatoneissuperiortothe others;
ifthe patientis using a personal insulin pump, it shouldbe removed with mandatory immediate follow-on with IVES insulinatthestartoftheintervention;
monitoring of glycaemia by repeated measurement of blood sugar levels every 1–2hours and control of kalaemia every 4hours in the perioperative period under insulin. Measure-mentsshouldbecarriedoutinarterialorvenousbloodrather than in capillary blood using glycaemia readers, which overestimatebloodsugarlevels,especially inthepresenceof vasoconstrictionand in hypoglycaemia[39].Thus, a value of 0.7g/L(3.8mmol/L)onglycaemiareadersshouldbeconsidered ashypoglycaemiaandimposecorrectiveactionandverification ofthevaluebymeasurementinalaboratory;
allsolutes maybeusedintheperioperativeperiod,including Ringerlactate;
perioperativeglycaemiccontrolisconditionedbythree param-eters:thetypeofdiabetes,thepreoperativeglycaemiccontrol andthetypeofsurgery(practicalsheetsG,H,J,K,L).
2.2. ProtocolforIVESinsulintherapy(practicalsheetO)
WeproposeaprotocolforIVESinsulintherapydevelopedby the working party that can be used preoperatively and perioperatively in a continuous surveillance unit or ICU (Fig. 1). It can be used in all T1D and T2D patients or in cases of stress,hyperglycaemia in patients withoutdiagnosed diabetes.
3. Additionalprinciplesofmanagement 3.1. Prophylaxisofnauseaandvomiting
Thepreventionofnauseaandvomitingisanessentialpartof theperioperativestrategy.Itisparticularlymoresoinadiabetic patient,takingintoaccounttheimportanceoftherapid resump-tionoffeeding.Inthiscontext,itisvalidtoproposeananaesthesia strategy that minimises the risk of nausea/vomiting (propofol rather than halogenated agents, avoid N2O, avoid reversal of
neuromuscularblockingagentswithneostigmine,favourRA)as wellasbroad-spectrumantiemetictherapy.Amongthepowerful antiemetic drugs that have beenvalidated in theperioperative period, dexamethasone carries therisk of hyperglycaemia.In a recent retrospective study, the authors evaluated the risk of hyperglycaemiaaccordingtothedoseofdexamethasoneused.As expected,adoseof8–10mgwasassociatedwithanincreasedrisk of hyperglycaemia when compared to a lower dose and the differenceinbloodsugarlevelswasstillsignificantinthisgroup during the first 24-h [40]. A dose of 8mg dexamethasone is considered tobemoreantiemetic thana doseof4mg [41]but exposes the patient to a higher risk of hyperglycaemia. We recommendtheuseof4mgdexamethasoneinassociationwith anotherantiemetic,suchasdroperidolora5-HT3antagonistdrug. 3.2. Treatmentofpain
Theeffectivemanagementofpostoperativepainisimportant. Poorlycontrolledpainisariskfactorforhyperglycaemia.Theusual
analgesicsdonotaffectglycaemiccontrolandcanbeusedwithout any modification of indication or dose. It has recently been demonstratedhoweverthatdiabeticpatientswithpoorglycaemic control (as measured by HbA1c level) have higher analgesic requirementsthanthosewithHbA1c<6.5%[42].TheuseofRA shouldbefavoured,whenpossible,asitisassociatedwithbetter controlofpostoperativepain.
3.3. Additionalmeasures
The degree of preoperative glycaemic control evaluated by HbA1c, the cessation of usual anti-diabetic treatments and preoperativefastinginthediabeticpatientwillallplayarolein theperioperativeglycaemicimbalance.Modulationof periopera-tiveinsulin resistanceis amajortherapeuticgoalasit helpsto significantly reducethe duration of postoperativehospital stay
[43].Thepreventionofhypothermia,theuseofRAandmultimodal analgesia (which will enable more rapid resumption of bowel movements),thelimitationofblood loss,earlyambulationand mini-invasivesurgeryareallmeasurestoprefer.
Thedogmaofprolongedpreoperativefastinghasrecentlybeen calledintoquestionbystudiesreportingthebeneficialeffectsof preoperativecarbohydrateadministrationonpostoperative insu-linresistanceinnon-diabeticpatients[43].Finally,diabetesdoes notaltertheusualrulesforantibioticprophylaxis.
Disclosureofinterest
Theauthorsdeclarethattheyhavenocompetinginterest. Themembersoftheworkingpartyhavereceivedsupportfrom theFrenchSociety of Anaesthesia and IntensiveCare Medicine (SFAR)andtheFrenchSocietyfortheStudyofDiabetes(SFD)for
transportandaccommodationwhennecessary.Thetwonational bodieshavealsoprovidedhonorariafortranslationofthetexts.
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