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Biochemia Medica 2007;17(1):1138

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Izvorni znanstveni lanak Original scientic article

Koncentracija glukoze i laktata u serumu bolesnika operiranih u totalnoj

intravenskoj anesteziji propofolom-fentanilom i u balansiranoj anesteziji

izouranom-fentanilom

Serum levels of glucose and lactate in patients treated under total intravenous

anesthesia with propofol-fentanyl and under balanced anesthesia with

isourane-fentanyl

Zlata Mujagi1, Elsada iko2, Vesna Vegar-Brozovi3, Mirsada Prao2

1Biokemijski laboratorij, Farmaceutski fakultet, Sveuilite u Tuzli, Tuzla, Bosna i Hercegovina

1Department of Biochemistry, School of Pharmacy, University of Tuzla, Tuzla, Bosnia & Herzegovina

2

Klinika za anesteziologiju i reanimaciju, Kliniki bolniki centar Tuzla, Tuzla, Bosna i Hercegovina2University Department of Anesthesiology and Resuscitation, Tuzla University Clinical Center, Tuzla, Bosnia & Herzegovina

3Klinika za anesteziologiju, reanimaciju i intenzivno lijeenje, Kliniki bolniki centar Zagreb, Zagreb

3University Department of Anesthesiology, Resuscitation and Intensive Care, Zagreb University Clinical Center, Zagreb, Croatia

Saetak

Uvod:Cilj studije bio je ut vrditi prije-, intra- i poslijeoperacijske koncentra-cije glukoze i laktata u serumu bolesnika podvrgnutih operacijskom zahvatuu donjem dijelu trbuha pod totalnom intravenskom anestezijom (TIVA) propo-folom-fentanilom odnosno opom izbalansiranom anestezijom izouranom-

fentanilom.Materi jali i metode: U ovu prospektivnu studiju bilo je ukljueno 50 boles-nika obaju spolova, u dobi od 35 do 60 godina, podvrgnutih operaciji donjegdijela trbuha. Bolesnici su nasumce podijeljeni u dvije skupine: eksperimental-nu skupinu od 25 bolesnika s ASA I/II (klasikacija Amerikog udruenja anes-teziologa) operiranih pod TIVA i kontrolnu skupinu od 25 bolesnika s ASA I/IIoperiranih pod izbalansiranom anestezijom. Dvije skupine nisu se znaajnorazlikovale prema duljini operacije i stupnju kirurke traume. Uzorci krvi zamjerenje glukoze i laktata uzimali su se u tono odreenim vremenskim to-kama: 30 minuta prije poetka operacije (T0), 30 minuta od poetka operacije(T1), na kraju operacije (T2), 2 sata nakon zavretka operacije (T3) i 24 sata na-kon zavretka operacije (T4). Serumske koncentracije glukoze i laktata mjerile

su se pomou testova dostupnih na tritu. Rezultati su se analizirali pomouMann-Whitneyevog testa.

Rezultati: Serumske koncentracije glukoze izmjerene u vremenskim toka-ma T1, T2 i T3 bile su znaajno nie (P = 0,03, P = 0,001 odnosno P < 0,001) ubolesnika operiranih uz TIVA propofolom-fentanilom nego u onih operiranihuz opu balansiranu anesteziju izouranom-fentanilom. Srednja koncentraci-ja laktata u krvotoku izmjerena u toki T4 bila je znaajno nia (P = 0,001)kod bolesnika operiranih uz TIVA nego u bolesnika operiranih uz balansiranuanesteziju, dok je lak tat u T1 bio nii u bolesnika operiranih uz balansiranuanesteziju (P = 0,01). U skupini bolesnika operiranih uz balansiranu anestezi-ju srednje serumske koncentracije glukoze i laktata izmjerene u T1, T2 i T3 bilesu znaajno vie od njihovih bazalnih koncentracija (P < 0,001). Koncentracije

Abstract

Background: To determine pre-, intra- and postoperative serum glucose andlactate concentrations in patients subjected to low abdominal surgery undertotal intravenous anesthesia (TIVA) with propofol-fentanyl, and in those un-der general balanced anesthesia with isourane-fentanyl.

Materials and Methods: This prospective study included 50 patients of bo-th sexes, aged between 35 and 60 years, subjected to low abdominal surge-ry. Patients were randomly divided into two groups: experimental group of25 ASA I/II (American Society of Anesthesiologists I/II classication) patientstreated under TIVA, and control group of 25 ASA I/II patients treated underbalanced anesthesia. The length of surgery and the degree of surgical traumadid not differ signicantly between the two anesthesia groups of patients.Blood samples for glucose and lactate measurements were drawn at exacttime points: 30 minutes before the beginning of the surgery (T0), 30 minutesafter the beginning of the surgery (T1), at the end of the surgery (T2), 2 hoursafter the surgery (T3), and 24 hours after the surgery (T4). Serum levels of glu-cose and lactate were measured using commercially available kits. The results

were evaluated with nonparametric Mann-Whitney test.Results: Serum concentrations of glucose measured at T1, T2 and T3 timepoints in patients treated under TIVA with propofol-fentanyl were signican-tly lower (P = 0.03, P = 0.001 and P < 0.001, respectively) than those in pa-tients treated under general balanced anesthesia with isourane-fentanyl.The mean circulating level of lactate measured at T4 point in patients treatedunder TIVA was signicantly lower (P = 0.001) than that in patients treatedunder balanced anesthesia, while T1 lactate was lower in patients treated un-der balanced anesthesia (P = 0.01). The mean serum concentrations of glu-cose and lactate measured at T1, T2, and T3 points were signicantly higherrelated to their baseline levels in patients treated under balanced anesthesia(P < 0.001). Both T2 and T3 values of glucose were above the normal range.

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Mujagi Z. i sur. Glukoza i laktat u serumu uz TIVA i balansiranu anesteziju

Mujagi Z. et al. Serum glucose and lactate in TIVA and in balanced anesthesia


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glukoze izmjerene u T2 i T3 bile su iznad gornje granice normalnog raspona.U bolesnika na TIVA srednje serumske koncentracije glukoze izmjerene u T1,T2, T3 i T4 bile su znaajno vie (P < 0,001 odnosno P = 0,001) od njihovih ba-zalnih vrijednosti, ali su samo one izmjerene u T2 prelazile gornju normalnu

vrijednost. U ovih bolesnika su koncentracije laktata u serumu izmjerene u T1,T2, T3 i T4 bile znaajno vie (P < 0,001) od bazalne koncentracije.

Zakljuak. Dobiveni rezultati ukazuju na to da je metabolini odgovor na ki-rurki zahvat vjerojatno ublaen odnosno poboljan u bolesnika operiranih uzTIVA propofolom-fentanilom u usporedbi s onim kod bolesnika operiranih uzopu balansiranu anesteziju izouranom-fentanilom.

Kljune rijei:glukoza, laktat, operacija, anestezija propofolom-fentanilom,anestezija izouranom-fentanilom

The mean serum levels of glucose determined at T1, T2, T3, and T4 in patientsunder TIVA were signicantly higher (P < 0.001; P = 0.001) than the baselinelevel, however, only the level measured at T2 point exceeded the upper nor-mal value. Serum lactate levels measured at T1, T2, T3, and T4 were signican-

tly higher than the baseline level (P < 0.001) in patients under TIVA.Conclusions: The results obtained suggested the metabolic response to sur-gery to be probably attenuated and thus improved in patients treated underTIVA with propofol-fentanyl in comparison with that in patients treated un-der general balanced anesthesia with isourane-fentanyl.

Key words: glucose, lactate, surgery, propofol-fentanyl anesthesia, isoura-ne-fentanyl anesthesia

Pristiglo: 26. veljae 2007. Received: February 26, 2007

Prihvaeno: 5. travnja 2007. Accepted: April 5, 2007

Uvod

Odgovor na stres za vrijeme operacijskog zahvata mijenja

se pod utjecajem mnogih imbenika, ukljuujui teinu

i trajanje operacijske traume, operacijsku tehniku te vrst

anestezije. Podaci o uincima anestetskih i analgetinih

postupaka na metaboline odgovore na operaciju kod lju-

di raznoliki su, pa ak i proturjeni. Biokemijski imbenici

koji zapoinju, reguliraju i odravaju metabolini odgo-

vor na operaciju nisu u potpunosti utvreni.

Dokumentirane su promjene u metabolizmu proteina iglukoze tijekom i poslije operacijskog zahvata (1). Studije

su pokazale da se oksidacija endogenih aminokiselina i ot-

putanje aminokiselina iz mii a pojaavaju nakon abdo-

minalne operacije (1). Hiperglikemija je izrazito obiljeje

metabolinog odgovora izazvanog kirurkom traumom

(2). Hiperglikemija se povezuje sa stupnjem kirurke trau-

me i na nju vjerojatno utjee anestezijska tehnika. Dok in-

halirani anestetici imaju tek minimalan inhibicijski uinak

na odgovor na operacij ski stres, anestezija propofolom

ublaava intraoperacijski porast glukoze u plazmi tijekom

operacije (3,4).

Uinak tkivne kirurke traume i vrste anestezije na nepos-redan metabolini odgovor nije u potpunosti razjanjen.

Stoga je cilj ove studije bio ispitati uinak totalne intraven-

ske anestezije (TIVA) propofolom-fentanilom i balansira-

ne anestezije izouranom-fentanilom na koncentracije

glukoze i laktata u krvotoku kod bolesnika podvrgnutih

elektivnoj kirurgiji donjeg dijela trbuha.

Materijal i metode

Ispitanici

U ovu prospektivnu studiju bilo je ukljueno 50 bolesni-

ka (22 mukaraca i 28 ena, bijelaca, stanovnika tuzlanske

Introduction

Stress response to surgery is modulated by several facto-rs, including severity and duration of surgical trauma, sur-gical technique, and type of anesthesia. Data on the effec-ts of anesthetic and analgesic regimens upon metabolicresponses to surgery in humans are varying and even con-troversial. The biochemical factors initiating, regulatingand sustaining the metabolic res ponse to surgery havenot been fully identied.

Changes in the protein and glucose metabolism duringand after surgery have been documented (1). Endoge-nous amino acid oxidation and amino acid release fromthe muscle after abdominal surgery have been shownto increase (1). Hyperglycemia is a prominent feature ofthe metabolic response induced by surgical trauma (2).Hyperglycemia is related to the degree of surgical traumaand can be, probably, inuenced by the anesthetic tec-hnique. Whereas inhaled anesthetics exert only minimalinhibitory inuence on the sur gical stress response, pro-pofol anesthesia attenuates the intraoperative increase inplasma glucose (3,4).The effects of surgical tissue trauma and type of anesthe-

sia on the immediate metabolic response have not yetbeen fully claried. Hence, the aim of the present studywas to investigate the effect of total intravenous anesthe-sia (TIVA) with propofol-fentanyl and the effect of balan-ced anesthesia with isourane-fentanyl on the circulatinglevels of glucose and lactate in patients subjected to elec-tive low abdominal surgery.

Materials and methods

Patients

The prospective study included 50 patients (22 male and

28 female, Cau casians, residents of the narrow region in

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regije). Svi su bolesnici podvrgnuti kirurkom zahvatu u

donjem dijelu trbuha (40 operacija raka debelog crijeva

i 10 histerektomija) na Klinici za kirurgiju i traumatologiju

te na Klinici za enske bolesti Klinikog bolnikog centra

u Tuzli, Bosna i Hercegovina.Kriteriji za ukljuenje bolesnika u studiju bili su: elektivni

operacijski zahvat u donjem dijelu trbuhu, dob izmeu

35 i 60 godina, status ASA I/II (klasikacija I/II Amerikog

udruenja anesteziologa), podjednako trajanje operacije i

podjednak stupanj kirurke traume.

Kriteriji za iskljuenje bili su: metabolina, jetrena ili bub-

rena bolest, uzimanje lijekova koji utjeu na metaboli-

zam glukoze.

Studiju je odobrio struni savjet Medicinskog fakulteta

Sveuilita u Tuzli. Prije ukljuenja u studiju svi su bolesni-

ci potpisali obrazac za obavijeteni pristanak.

Bolesnici su nasumce podijeljeni u dvije skupine: eksperi-mentalnu skupinu od 25 bolesnika s ASA I/II operiranih uz

TIVA propofolom-fentanilom i kontrolnu skupinu od 25

bolesnika s ASA I/II operiranih uz opu balansiranu anes-

teziju izouranom-fentanilom.

Protokol anestezije

Protokol balansirane anestezije: za predmedikaciju mida-

zolam 0,1 mg/kg i.m.; za indukciju tiopental natrij 5 mg/

kg, uz fentanil 0,1 mg prije intubacije, u ukupnoj dozi od

0,005 mg/kg prije kirurke incizije; za odravanje anestezi-

je izouran 1,2-2,4 vol% pomijean s oksidulom i kisikom

u omjeru 1:1; suksametonium hidroklorid 1,5 mg/kg i Trac-

rium 0,5-0,8 mg/kg za intubaciju i miorelaksaciju.Protokol za TIVA: za predmedikaciju midazolam 0,1 mg/

kg i.m.; za indukciju propofol 2 mg/kg i fentanil 0,1 mg

prije intubacije, u ukupnoj dozi od 0,005 mg/kg prije ki-

rurke incizije; za odravanje anestezije infuzija propofo-

la 6-12 mg/kg/h uz ventilaciju naizmjeninim pozitivnim

tlakom (IPPV) mjeavine zraka, kisika i FiO233-50%; opeto-

vane doze fentanila od 0,1 mg ovisno o klinikim pokaza-

teljima; suksametonium hidroklorid 1,5 mg/kg i Tracrium

0,5-0,8 mg/kg za intubaciju i miorelaksaciju.

Tijekom operacijskog zahvata u svih se je bolesnika pro-

vodio hemodinamski nadzor (srani ritam, sistolini i dijas-

tolini krvni tlak) i praenje CO2u izdahu. Tijekom opera-cije bolesnici su primali izbalansiranu otopinu elektrolita

te Ringerovu otopinu laktata i 5%-tnu otopinu glukoze 24

sata poslije operacije. Srani ritam, krvni tlak i proirenost

zjenica bili su vani pokazatelji u praenju tijeka anestezi-

je. Anestetici i miorelaksansi dodavani su prema protoko-

lu tijekom operacijskog zahvata.

Uzorci

Uzorci krvi za mjerenje koncentracije glukoze i laktata uzi-

mali su se u tono odreeno vrijeme, tj. 30 minuta prije

poetka operacije (T0), 30 minuta od poetka operacije

(T1), na kraju operacije (T2), 2 sata nakon operacije (T3) i 24

Tuzla surrounding). All of them were subjected to the low

abdominal surgery (40 colon cancer operations and 10 hyste-rectomies) at University Department of Surgery and Trauma-

tology and University Department of Gynecology, Tuzla Uni-

versity Clinical Center, Tuzla, Bosnia and Herzegovina.The inclusion criteria for patients were as follows: electi-ve low abdominal surgery; age between 35 and 60 years;

ASAI/II status (American Society of Anesthesio logists I/II

classication); almost the same length of the surgery, andalmost the same degree of surgical trauma.

Exclusion criteria were as follows: presence of a metabo-lic, hepatic or renal disease, and receiving any medication

known to affect glucose metabolism.

The study was approved by the Council of the School ofMedicine, University of Tuzla. All patients signed infor-

med consent forms before inclusion in the study.Patients were randomly divided into two groups: experi-

mental group of 25 ASA I/II patients treated under TIVAwith propofol-fentanyl, and control group of 25 ASA I/II

patients treated under general balanced anes thesia with

isourane-fentanyl.

Anesthesia protocol

The protocol of balanced anesthesia was as follows: pre-

medication with midazolam 0.1 mg/kg i.m.; induction wi-

th thiopental sodium 5 mg/kg, with fentanyl 0.1 mg befo-

re intubation with the overall dose of 0.005 mg/kg before

surgical incision; maintenance of anesthesia with isoura-

ne 1.2-2.4 vol% mixed with nitrous oxide and oxygen at a

ratio of 1:1; suxamethonium hydrochloride 1.5 mg/kg andTracrium 0.5-0.8 mg/kg for intubation and myorelaxation.

The protocol for TIVA was as follows: premedication with

midazolam 0.1 mg/kg i.m.; induction with propofol 2 mg/

kg and fentanyl 0.1 mg before intubation with the overall

dose of 0.005 mg/kg before surgical incision; maintenan-

ce of anesthesia with propofol infusion 6-12 mg/kg/h wi-

th ventilation by intermittent positive pressure (IPPV) wi-

th a mixture of air, oxygen and FiO233-50%; repetitive fen-

tanyl doses of 0.1 mg depending on clinical para meters;

suxamethonium hydrochloride 1.5 mg/kg and Tracrium

0.5-0.8 mg/kg for intuba tion and myorelaxation.

Hemodynamic monitoring (heart rate, systolic and diasto-lic blood pressure) and expired air CO

2 monitoring were

performed in all patients during sur gical treatment. Patien-

ts received electrolyte-balanced solution during the ope-

ration, and Ringer-lactate solution and 5% glucose solution

24 hours after the operation. Heart rate, blood pressure and

pupillary dilatation were re levant parameters for the anesthe-

sia course follow up. Anesthetics and myorelaxants were ad-

ded according to the protocol during the operation.

Samples

Blood samples for glucose and lactate measurements

were drawn at exact time points: 30 minutes before the

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sata nakon operacije (T4). Koncentracija glukoze u serumu

mjerila se pomou testa Glucose Flex(Dade Behring), a

koncentracija laktata pomou testa Lactic Acid Flex(Da-

de Behring) dostupnih na tritu.

Statistika analiza

Raspodjela kvantitativnih varijabla utvrena je pomou

distribucijskih histograma uz unoenje vjerojatnosti i vje-

rojatnosti lienih trenda. Rezultati su se procjenjivali po-

mou neparametrijskog Mann-Whitneyevog testa, uz iz-

raunavanje srednjih vrijednosti, standardnih devijacija

(SD) i standardnih pogrjeaka (SE). Razina statistike zna-

ajnosti utvrena je kao vrijednost P = 0,05. Sve statisti-

ke analize provedene su pomou statistikog programa

SPSS verzija 10.

RezultatiPrema testovima upotrebljenim za odreivanje glukoze i

laktata normalan raspon za glukozu bio je 3,9-6,1 mmol/

L, a za laktat 0,4-2,0 mmol/L. Srednje serumske koncentra-

cije glukoze izmjerene u T1, T

2i T

3bile su iznad normalnog

raspona za glukozu u bolesnika operiranih uz balansiranu

anesteziju izouranom-fentanilom, dok su koncentracije

izmjerene u T0 i T

4bile unutar normalnog raspona. U bo-

lesnika operiranih uz TIVA propofolom samo je serumska

koncentracija glukoze izmjerena u T2 bila iznad normal-

nog raspona, dok su sve ostale vrijednosti bile unutar nor-

malnog raspona za glukozu.

U bolesnika operiranih uz balansiranu anesteziju srednjaserumska koncentracija laktata izmjerena u T

2bila je iznad

normalnog raspona za laktat, dok su sve ostale izmjerene

vrijednosti bile unutar referentnog raspona. U bolesnika

operiranih uz TIVA propofolom sve srednje koncentracije

laktata u serumu izmjerene u T1, T

2, T

3i T

4bile su unutar

normalnog raspona za laktat.

Srednje serumske koncentracije glukoze izmjerene u T1,

T2 i T

3bile su znaajno nie u skupini bolesnika operira-

nih uz TIVA propofolom-fentanilom u usporedbi s boles-

nicima koji su operirani uz balansiranu anesteziju izoura-

nom-fentanilom (P = 0,03, P = 0,001 odnosno P < 0,001)

(tablica 1.).Srednja koncentracija laktata u krvotoku izmjerena u T

4u

skupini bolesnika operiranih uz TIVA bila je znaajno nia

u usporedbi s onom kod bolesnika operiranih uz balansi-

ranu anesteziju izouranom (P = 0,001), dok je koncentra-

cija laktata izmjerena u T1bila nia u skupini boles nika na

balansiranoj anesteziji nego u onih na TIVA (P = 0,01) (tab-

lica 2.).

beginning of the surgery (T0), 30 minutes after the begin-

ning of the surgery (T1), at the end of the surgery (T

2), 2

hours after the surgery (T3), and 24 hours after the surge-

ry (T4). Serum levels of glucose were measured using a

commercially available Glucose FlexTM

kit (Dade Behring).Serum levels of lactate were measured using a commer-

cially available Lactic Acid FlexTM kit (Dade Behring).

Statistical analysis

The distribution of quantitative variables was determined

by using distribution histograms with probability plots

and de-trended probability plots. The results were evalua-

ted with nonparametric Mann-Whitney test, with mean

values, standard deviations (SD), and standard errors (SE)

calculated. The value of P = 0.05 was considered statisti-

cally signicant. All statistical analyses were performed

with SPSS statistical software, version 10.

Results

According to the kits used for glucose and lactate determi-

nation, the normal range for glucose was 3.9-6.1 mmol/L,

and for lactate 0.4-2.0 mmol/L. The mean serum concen-

trations of glucose measured at time points T1,T

2, and T

3

were all above the normal range for glucose in patients

treated under balanced anesthesia with isourane-fen-

tanyl, while the T0

and T4

values were within the normal

range. Only the T2

glucose concentration was above the

normal range in patients treated under TIVA with propo-

fol, while other values were within the normal range forglucose.

The mean se rum level of lactate measured at T2

was abo-

ve the normal range in patients treated under balanced

anesthesia, while lactate values at other points were wit-

hin the reference range. Lacta te concentrations measu-

red at T1,T

2,T

3and T

4were within the normal range in pa-

tients treated under TIVA with propofol.

The mean serum levels of glucose measured at T1,T

2, and

T3

time points in patients operated under TIVA with pro-

pofol-fentanyl were signicantly lower than those in pa-

tients treated under general balanced anesthesia with

isourane-fentanyl (P = 0.03, P = 0.001 and P < 0.001, res-pectively) (Table 1).

The mean circulating levels of lactate measured at T4

in

TIVA group of patients was signicantly lower in compari-

son with that in patients treated under balanced anesthe-

sia with isourane (P = 0.001), while serum lactate deter-

mined at T1point in the balanced anesthesia group was

lower than that in TIVA group (P = 0.01) (Table 2).

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Rasprava

Rezultati ovoga ispitivanja su pokazali da su srednje se-

rumske koncentracije glukoze i laktata za vrijeme i ne-

posredno nakon operacije znaajno nie u bolesnika

operiranih uz TIVA propofolom-fentanilom u usporedbi

s bolesnicima operiranim uz opu balansiranu anestezi-

ju izouranom-fentanilom (tablice 1. i 2.). Dobiveni rezul-

tati ukazuju na to da se metabolini odgovor na kirurki

zahvat vjerojatno ublaava i time poboljava u bo lesnika

operiranih uz TIVA propofolom-fentanilom u odnosu na

onaj u bolesnika operiranih u opoj balan siranoj aneste-

ziji izouranom-fentanilom. Rezultati nekih drugih slinih

studija sukladni su rezultatima dobivenim u ovom naem

ispitivanju. Za razliku od inhalirane anestezije, anestezija

propofolom uz dodatak sufentanila obuzdava intraope-

racijski porast koncentracije glukoze u plazmi (4). Inhibi-

cijski uinak propofola na simpatoadrenalni sustav doku-

mentiran je u bolesnika podvrgnutih operaciji srca (5),

kao i in vitrokad su koncentracije propofola, slino onimazabiljeenim za vrijeme uvoenja u anesteziju, smanjile

bazalno i nikotinom poticano otputanje katekolamina iz

kromanskih stanica (5). TIVA propofolom ublaava perio-

peracijski metabolini i endokrini odgovor u usporedbi s

inhaliranom anestezijom sevouranom (6). Intraoperacij-

TABLICA1. Serumske koncentracije glukoze (mmol/L) u bolesni-ka operiranih uz TIVA propofolom-fentanilom i bolesnika operi-

ranih uz balansiranu anesteziju izouranom-fentanilom u odre-

enim vremenskim tokama

TABLE1. Circulating glucose levels (mmol/L) in patients treatedunder TIVA with propofol-fentanyl and patients treated under

balanced anesthesia with isourane-fentanyl at different time

points

TABLICA 2. Serumske koncentracije laktata (mmol/L) u boles-nika operiranih uz TIVA propofolom-fentanilom i bolesnika ope-

riranih uz balansiranu anesteziju izouranom-fentanilom u od-reenim vremenskim tokama

TABLE2. Circulating lactate levels (mmol/L) in patients treatedunder TIVA with propofol-fentanyl and patients treated under

balanced anesthesia with isourane-fentanyl at different timepoints

Discussion

The results of this study showed the mean serum con-

centrations of glucose and lactate during the operation

and shortly after the operation to be signicantly lower

in patients treated under TIVA with propofol-fentanyl in

comparison with those in patients treated under gene-

ral balanced anesthesia with isourane-fentanyl (Tables

1 and 2). The results suggested the metabolic response

to surgery to be probably attenuated and thus improved

in patients treated under TIVA with propofol-fentanyl as

compared with that in patients treated under general ba-

lanced anesthesia with isourane-fentanyl. Results of so-

me other similar studies are comparable with those obtai-

ned in our study. Propofol anesthesia supplemented with

sufentanil, in contrast to inhaled anesthesia, suppressed

the intraoperative increase in plasma glucose concen-

tration (4). Inhibitory effects of propofol on the sympat-

hoadrenal system have been documented in patients

undergoing cardiac surgery (5), and documented in vitrowhen propofol concentrations, similar to those observed

during the induction of anesthesia, decreased the basal

and nicotine-stimulated release of catecholamines from

chromaffi n cells (5). TIVA with propofol blunts periopera-

tive metabolic and endocrine response when compared

Patient group -30 min +30 min +180 min +300 min +1440 min

TIVA (N = 25) 4.6 0.09** 5.79 0.13 6.63 0.17 5.82 0.10 5.08 0.07

Balanced anesthesia (N = 25) 5.005 0.14 6.19 0.16 7.53 0.18 8.57 0.30 5.18 0.15

p* 0.6 0.03 0.001 < 0.001 0.7

TIVA, total intravenous anesthesia; *Mann-Whitney test; **x SE

Patient group -30 min +30 min +180 min +300 min +1440 min

TIVA (N = 25) 1.140.04** 1.62 0.05 2.10 0.06 1.52 0.06 0.67 0.03

Balanced anesthesia (N = 25) 0.87 0.5 1.37 0.05 2.10 0.09 1.68 0.09 0.89 0.04

p* 0.06 0.01 0.6 0.1 0.001

TIVA, total intravenous anesthesia; *Mann-Whitney test; **xSE

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ske koncentracije glukoze, laktata i slobodnih masnih ki-

selina u plazmi bile su znaajno nie uz TIVA u usporedbi

s inhalacijskom anestezijom (7). Anestetici mogu utjecati

na metabolizam glukoze, barem djelomice, kroz modula-

ciju simpatikog tonusa.Intraoperacijske koncentracije glukoze mjerene 2 sata na-

kon operacije bile su iznad normalnog raspona u naih bo-

lesnika operiranih uz anesteziju izouranom-fentanilom,

dok je u bolesnika operiranih uz TIVA propofolom samo

koncentracija glukoze izmjerena u T2bila iznad tog raspo-

na, a sve druge izmjerene koncentracije glukoze bile su

ununtar normalnog raspona. Koncentracije laktata mje-

rene u svim vremenskim tokama u objema skupinama

bolesnika bile su unutar referentnog raspona, s iznimkom

koncentracije laktata izmjerene u T2

u skupini bolesnika

na balansiranoj anesteziji. Ovi su nalazi sukladni s literatur-

nim podacima (4,8-12).

Pretpostavlja se da su mehanizmi kojima se posreduju

metabolini utjecaji anestezije vjerojatno hormonski (8).

Stresni hormon kortizol je snaan promicatelj glukoneo-

geneze u jetri (13), te djeluje na jetrene zalihe glikogena

kao i na smanjenje utroka glukoze u perifernim tkivima.

Hormon rasta i prolaktin imaju stanovitu ulogu u stresu,

vjerojatno kroz njihovo hiperglikemijsko djelovanje u jet-

ri (13,14). Anestezija propofo lom nije znaajno utjecala na

svetjelesnu sintezu i oksidaciju proteina, ali je uzrokovala

manje no znaajno snienje svetjelesne razgradnje protei-

na, mogue posredovano sniavanjem koncentracije kor-

tizola u plazmi (15).

Nadalje, neki podaci ukazuju na to da anestetske koncen-

tracije propofola inhibiraju stvaranje O2uslijed preopte-

reenja glukozom, a to bi se moglo odvijati kroz mehaniz-

me koji ukljuuju, barem djelomice, suzbijanje staninog

preuzimanja glukoze (16).

Razgradnja proteina u skeletnim miiima, glikoliza i glu-

koneogeneza su istaknuta obiljeja intermedijarnog me-

tabolizma kod bolesnika u uvjetima kirurkog stresa. Za-

paen je izravan odnos izmeu svetjelesne razgradnje

proteina i proizvodnje glukoze kod kirurkih bolesnika

(3,9,17). Miini proteini razgrauju se kako bi osigurali

glukoneogenine aminokiseline za de novo glukoneoge-

nezu u jetri. Poticanje glukoneogeneze kortizolom u jet-ri uzrokovano je prvenstveno stimulacijom katabolizma

proteina (13,18). Kinetika ispitivanja metabolizma protei-

na i glukoze za vrijeme abdominalne kirurgije otkrila su

snienje svetjelesnog metabolizma proteina i glukoze, uz

hiperglikemijski odgovor uzrokovan smanjenim svetjeles-

nim klirensom glukoze, kao i znaajnim odnosom izmeu

proizvodnje gluko ze i razgradnje proteina (9). Stopa sveu-

kupnog metabolizma po veana je u stanjima stresa, ali je

kapacitet oksidativnog metabolizma ogranien. To je je-

dan od glavnih razloga zbog kojeg se katabolini putovi

poinju odvijati na neaerobian nain i stvarati, izmeu

ostalog, laktat.

to inhaled anesthesia with sevourane (6). Intraoperative

plasma concentrations of glucose, lactate and free fatty

acids were signicantly lower in TIVA in comparison with

inhalation anesthesia (7). Anesthetic agents can affect glu-

cose metabolism through, at least partly, sympathetic to-ne modulation.

Intraoperative glucose levels and that measured two hou-

rs after the surgery in our isourane-fentanyl anesthesia

group were above the normal range for glucose; howe-

ver, in patients treated under TIVA with propofol, only T2

glucose concentration was above the normal range while

the levels measured at other points were within the nor-

mal range. Lactate levels measured at all points in both

patient groups, except for T2

in balanced anesthesia,we-

re within the reference range. The se ndings are in accor-

dance with some other literature reports (4,8-12).

It has been proposed that the mechanisms by which the

metabolic effects of anesthesia are mediated are likely to

be hormonal (8). The stress hormone cortisol is a powerful

promoter of gluconeogenesis in the liver (13), and acts on

the glycogen storage in the liver as well as on the reduc-

tion of glucose utilization in peripheral tissues. Growth

hormone and prolactin have a role in stress, probably by

their hyperglycemic action in the liver (13,14). Propofol

anesthesia did not signicantly affect whole body protein

synthesis and oxidation but caused a small, although sig-

nicant, decrease in the whole body protein breakdown,

possibly mediated through the suppression of plasma

cortisol concentration (15). Furthermore, some data indi-

cate that anesthetic concentrations of propofol inhibit

O2-generation by D-glucose overload, and that this may

occur viamechanisms that include, at least in part, the in-hibition of cellular glucose uptake (16).

Protein degradation in skeletal muscle, glycolysis, and

gluconeogenesis are the prominent characteristics of in-

termediary metabolism in patien ts under surgical stress

conditions. Direct relationship between the whole body

protein breakdown and glucose production in surgical

patients have been observed (3,9,17). Muscle proteins are

broken down to provide gluconeogenic amino acids for

de novogluconeogenesis in the liver. Promotion of gluco-

neogenesis by cortisol in the liver is caused primarily bythe stimulation of protein catabolism (13,18). Kinetics stu-

dies of protein and glucose metabolism during abdomi-

nal surgery have revealed depression of the whole body

protein and glucose metabolism with the hyperglycemic

response being caused by a decreased whole body glu-

cose clearance and a signicant relationship between glu-

cose production and protein breakdown (9). The rate of

the overall metabolism is increased in stress conditions,

but the capacity of oxidative metabolism is limited. This

is one of the main reasons why catabolic pathways begin

to work unaerobically and to produce, among other meta-

bolites, lactate.

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77

Rezultati zabiljeeni u ovom istraivanju pokazali su da

su serumske koncentracije glukoze i laktata poviene ti-

jekom operacijskog zahvata, te da je taj porast izraeniji u

bolesnika koji su operirani uz opu balansiranu anesteziju

izouranom u usporedbi s onima koji su operirani uz TIVApropofolom. Zapaene promjene vjerojatno su uzrokova-

ne kirurkim stresom, katabolizmom proteina i glukoneo-

genezom. Meutim, u dvjema anestezijskim skupinama

bolesnika ispitivali smo samo dva metabolina paramet-

ra. To je bilo znatno ogranienje ove nae studije, jer nije

bilo mogue tono procijeniti koji je proces odgovorniji

za kontrolu glikemije u skupini bolesnika s TIVA.

Metabolini odgovor na operaciju vjerojatno je ublaen

i time poboljan u bolesnika operiranih uz TIVA propofo-

lom u usporedbi s onim u bolesnika operiranih uz opu

balansiranu anesteziju izouranom. Nai su rezultati suk-

ladni literaturnim podacima iz slinih studija i pokazuju

kako viestruki pristupi uz kombinaciju anestetika, anal-

getika i operacijskih strategija rezultiraju boljom regulaci-

jom glikemije tijekom intra- i perioperacijskog razdoblja,

a time i boljim klinikom ishodom u bolesnika.

Zahvale

Zahvaljujemo prof. dr. Hamzi Mujagiu, dr. sci., na vrlo ko-

risnim savjetima u oblikovanju studije i statistikoj obradi

rezultata. Takoer zahvaljujemo osoblju Klinike za kirurgi-

ju, Klinike za enske bolesti i Biokemijskog laboratorija Kli-

nikog bolnikog centra u Tuzli, Bosna i Hercegovina, zatehniku pomo u provedbi studije.

Results obtained in our study showed that serum leve-

ls of glucose and lactate were increased during surgical

treatment, and that this increase was more pronounced

in patients treated under general balanced anesthesia wi-

th isourane than in those under TIVA with propofol. Theobserved changes are probably due to surgical stress, pro-

tein catabolism and gluconeogenesis. However, only two

metabolic parameters were investigated in the two anes-

thesia groups of our patients. It was a major limitation to

our study because it was not possible to precisely evalua-

te which process was more responsible for the control of

glycemia in TIVA group of patients.

Metabolic response to surgery is probably attenuated

and thus improved in patients treated under TIVA with

propofol in comparison with that in patients treated un-

der general balanced anesthesia with isourane. Our re-

sults are in accordance with similar data reported in the

relevant literature, and they indicate that multimodal ap-

proaches combining anesthetic, analgesic and surgical

strategies will result in better control of glycemia during

the intra- and perioperative periods, and thus in improve-

ment of the clinical outcome of disease.

Acknowledgments

We thank Prof. Hamza Mujagi, MD, PhD, for his very use-

ful suggestions in the study desi gn and statistical analysis

of the results. We also thank the staff of the University

Department of Surgery, University Department of Gyne-cology, and Department of Bioche mistry, Tuzla University

Clinical Center, Tuzla, Bosnia and Herzegovina, for their tec-

hnical assistance during the study.

Literatura/References

1. Schricker T. The catabolic response to surgery: how can it be modiedby the anesthesiologist? Can J Anesth 2001;48:R1-R5.

2. Schricker T, Lattermann R, Schreiber M, Geisser W, Georgieff M, Rader-macher P. The hyperglycaemic response to surgery: pathophysiology,clinical implications and modication by the anaesthetic technique.Clin Intern Care 1998;9:118-28.

3. Kocamanoglu IS, Sahinoglu AH, Tr A, Baris S, Karakaya D. The compa-

rison of the effects of TIVA and inhalation anaesthesia on hemodyna-

Adresa za dopisivanje:

Zlata Mujagi

Biokemijski laboratorij

Farmaceutski fakultet Sveuilita u Tuzli

Univerzitetska 1

75000 Tuzla

Bosna i Hercegovina

e-pota: [email protected]

tel: +387 35 320 628; +387 61 729 001faks: +387 35 320 991

Corresponding author:

Zlata Mujagic

Department of Biochemistry

School of Pharmacy, University of Tuzla

Univerzitetska 1

75000 Tuzla

Bosnia & Herzegovina

e-mail: [email protected]: +387 35 320 628; +387 61 729 001

fax: +387 35 320 991

mic conditions, metabolic-endocrine response to trauma and musclerelaxant consumption. Turk Anestez Reanim 2000;28:452-6.

4. Schricker T, Carli F, Schreiber M, Wachter U, Geisser W, Lattermann R,et al. Propofol/sufentanil anesthesia suppresses the metabolic and en-docrine response during, not after, lower abdominal surgery. AnesthAnalg 2000;90:450-5.

5. Ng A, Tan SSW, Lee HS, Chew SL. Effect of propofol infusion on the en-

docrine to cardiac surgery. Anaesth Intens Care 1995;23:543-7.

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