UNIQUE FEATURES AND DIFFERENCES BETWEEN ADULT AND PEDIATRIC CARDIOPULMONARY BYPASS DURING CARIAC SURGERY PROCEDURES

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1 VTK TOKOM KARDIOHIRURŠKIH PROCEDURA KOD DECE I ODRASLIH Revijalni članak UDK Critical Rewiev SPECIFIČNOSTI I RAZLIKE VANTELESNOG KRVOTOKA TOKOM KARDIOHIRURŠKIH PROCEDURA KOD DECE I ODRASLIH UNIQUE FEATURES AND DIFFERENCES BETWEEN ADULT AND PEDIATRIC CARDIOPULMONARY BYPASS DURING CARIAC SURGERY PROCEDURES Dragana Unić-Stojanović, 1 Miroslav Miličić, 2 Petar Vuković, 2 Dejan Marković, 3,4 Miomir Jović 1,3 Dragana Unić-Stojanović, 1 Miroslav Miličić, 2 Petar Vuković, 2 Dejan Marković, 3,4 Miomir Jović 1,3 1 Klinika za anesteziju i intenzivno lečenje, Institut za kardiovaskularne bolesti Dedinje, Beograd 2 Klinika za kardiohirurgiju, Institut za kardiovaskularne bolesti Dedinje, Beograd 3 Medicinski fakultet Univerziteta u Beogradu 4 Klinika za kardiohirugiju, Klinički centar Srbije, Beograd 1 Clinic for anesthesiology and intensive therapy, Institute for cardiovascular deseasse Dedinje, Belgrade 2 Clinic for cardiosurgery, Institute for cardiovascular deseasse Dedinje, Belgrade 3 School of medicine, Belgrade University 4 Clinic for cardiosurgery, Clinical Center of Serbia, Belgrade Sažetak. Mada su principi pedijatrijske i adultne anestezije u srčanoj hirurgiji slični, nekoliko značajnih razlika postoje. Većina razlika pedijatrijskog i adultnog vantelesnog krvotoka se može objasniti postojanjem anatomskih, metaboličkih i fizioloških razlika ove dve grupe bolesnika. Tokom vantelesnog krvotoka (VTK), odrasli bolesnici su za razliku od pedijatrijskih bolesnika retko izloženi biološkim ekstremnim okolnostima. U adultnih bolesnika, temperatura se retko snižava ispod 25ºC, hemodilucija je značajno umerenija, perfuzioni pritisak se uobičajeno održava između 50 i 80 mmhg, protok na pumpi za vantelesni krvotok se održava u opsegu od 50 do 65 ml/kg/min i ph menadžment je manje značajan zbog korišćenja umerene hipotermije i retke primene cirkulatornog aresta. Venske i arterijske kanile su velike i manje deformišu pretkomoru i aortu i njihovo pozicioniranje je predvidljivije. U pedijatrijskih bolesnika uobičajeno se koriste duboka hipotermija (15-20ºC), izražena hemodilucija (3 do 15 puta veća dilucija cirkulišuće krvi), nizak perfuzioni pritisak (20-30 mmhg), velike varijacije u veličini protoka krvi tokom vantelesnog krvotoka (od 200 ml/kg/min do totalnog cirkulatornog aresta) i različit pristup Summary. Although many of the principles governing modern pediatric cardiovascular anesthesia are similar to those that guideanesthetic management of the adult cardiac patient, several important differences do exist. Major differences adult and pediatric cardiopulmonary bypass (CPB) stem from anatomic, metabolic, and physiologic differences in these 2 groups of patients. During CPB, adultpatients are infrequently exposed to these biologic extremes seen in pediatric patients.in adult cardiac patients, temperature is rarely lowered below 25 C, perfusion pressure is generally maintained at 50 to 80 mm Hg, hemodilution is more moderate, flow rates are maintained at 50 to 65 ml/kg/min, and ph management strategy is less influential because of moderate hypothermic temperatures and rare use of circulatory arrest. Venous and arterial cannulas are larger and less deforming of the atriaand aorta, and their placement is more predictable. In pediatric patients, there is often use of deephypothermia (15 20 C), low perfusion pressures (20 30 mm Hg), wide variation in pump flow rates (ranging from highs of 200 ml/ kg/min to total circulatory arrest),hemodilution (3- to 15-fold greater dilution of circulating blood volu- Adresa autora: Dragana Unić-Stojanović, Institut za kardiovaskularne bolesti Dedinje, Milana Tepića 1,Beograd, tel: 064/ ; dunic@yubc.net

2 256 SJAIT 2012/3-4 regulaciji ph (alfa-stat ili ph-stat ili oba sekvencijalno). Mada globalno posmatrano sličan, sistem za VTK u dece je značajno različit od onog u adultnoj populaciji. me), and differing blood ph management techniques (alpha-stat or ph-stat, or both sequentially). Although superficially similar, the conduct of CPB in children is considerably different from that in adults. Ključne reči: vantelesni krvotok, razlike; kardijalna hirurgija, odrasli, pedijatrijski bolesnici Key words: cardiopulmonary bypass, differences; cardiac surgery, pediatrics, adult Uvod Mada su većina principa pedijatrijske i adultne anestezije u srčanoj hirurgiji slični, nekoliko značajnih razlika postoje. Jedinstvenost kardiovaskularne anestezije u dece potiče od nekih karakteristika pedijatrijskih bolesnika, dijagnostikovanog kongenitalnog srčanog oboljenja i same hirurške intervencije. Cilj našeg rada je da prikažemo osnovne karakteristike i razlike između vantelesnog krvotoka (VTK) u pedijatrijskoj i adultnoj srčanoj hirurgiji. Hirurške procedure U pedijatrijskih bolesnika sa kongenitalnim srčanim manama, kardiovaskularni sistem je jedini uzrok zdravstvenih problema 1. To je u suprotnosti sa multiplim dijagnozama i bolestima različitih organa i sistema organa u adultnoj populaciji sa stečenim kardiovaskularnim oboljenjima. U poređenju sa kardiohirurškim procedurama u odraslih bolesnika, hirurška korekcija kongenitalnih srčanih oboljenja se odlikuje ekstenzivnijom intrakardijalnom hirurgijom sa vrlo čestim hirurškim pristupom kroz desnu pretkomoru i komoru. U većini hirurških procedura neophodno je potpuno mirno i bezkrvno operativno polje koje se nekada teško postiže zbog prisustva intrakardijalnih ili ekstrakardijalnih šantova, aortopulmonalnih kolaterala ili povećanog plućnog venskog protoka. Razlike adultnog i pedijatrijskog vantelesnog krvotoka Većina razlika pedijatrijskog i adultnog vantelesnog krvotokase može objasniti postojanjem anatomskih, metaboličkih i fizioloških razlika ove dve grupe bolesnika (Tabela 1.). U kongenitalnoj kardiohirurgiji, sistem za VTK je prilagođen za primenu u bolesnika različitog uzrasta i telesne težine, od 1.5 kg u prevremeno rođenih infanta do 100 kg u adolescenata. 2 Fiziološki efekti VTK na novorođenčad i decu su različiti od efekata na odrasle. Tokom VTK, pedijatrijski bolesnici su, za razliku od odraslih bolesnika, izloženi biološkim ekstremnim okolnostima, kao što su duboka hipotermija (15-20ºC), hemodilucija (3 do 15 puta veća dilucija cirkulišuće krvi), nizak perfuzioni pritisak (20-30 mmhg), velike varijacije u veličini protoka Tabela 1.Razlike između pedijatrijskih i adultnih bolesnika Razlike između pedijatrijskih i adultnih bolesnika Manji cirkulišući volumen krvi Viša potrošnja kiseonika Reaktivno plućno vaskularno korito Prisustvo intra i ekstrakardijalnih šantova Nezreli organi i sistemi organa Izmenjena termoregulacija Loša tolerancija mikroembolizacija

3 VTK TOKOM KARDIOHIRURŠKIH PROCEDURA KOD DECE I ODRASLIH krvi tokom VTK (od 200 ml/kg/min do totalnog cirkulatornog aresta) i različit pristup u regulacijiph (alfa-stat ili ph-stat ili oba sekvencijalno) 1. Nasuprot pedijatrijskim bolesnicima, adultni bolesnici se retko izlažu takvim ekstremnim situacijama. U adultnih bolesnika, temperatura se retko snižava ispod 25ºC, hemodilucija je značajno umerenija, perfuzioni pritisak se uobičajeno održava između 50 i 80 mmhg, protok pumpe za VTK se održava u opsegu od 50 do 65 ml/kg/min i ph menadžment je manje značajan zbog korišćenja umerene hipotermije i retke primene cirkulatornog aresta. Suplementacija glukozom je retko problem kod odraslih bolesnika zbog velikih depoa glikogena u jetri. Venske i arterijske kanile su velike i manje deformišu pretkomoru i aortu i njihovo pozicioniranje je predvidljivije. U tabeli 2 su prikazane osnovne razlike između pedijatrijskog i adultnog VTK. 1. Hemodilucija Relativno velika zapremina prajminga u sistemu za VTK u odnosu na zapreminu cirkulišuće krvi u infanta i dece vodi značajnoj hemodiluciji. U odraslih zapremina prajminga je ekvivalentna 25 do 33% zapremine cirkulišuće krvi, dok u neonatusa i infanta, zapremina prajminga i za 200% prevazilazi zapreminu cirkulišuće krvi. 257 Takođe, zbog disproporcionalno velikog odnosa zapremine prajminga i zapremine cirkulišuće krvi u dece,od posebnog značaja je sastav rastvora za prajming u aparatu za pedijatrijski VTK. Glavni sastavni elementi prajminga su kristaloid, krv (u cilju održanja zavisno od telesne temperature podesnog nivoa hemoglobina i hematokrita) i koloid1. Pedijatrijski prajming rastvori uobičajeno sadrže varijabilan nivo elektrolita, kalcijuma, glukoze i laktata. Zapravo, sadržaj elektrolita, kalcijuma i laktata je značajno viši ako se u prajming dodaje transfuzija pune krvi, odnosno značajno je niži ako se krv ne dodaje. Za razliku od odraslih, u infanta se vrlo često u prajming dodaje koloid (albumini, radi održavanja koloidno-osmotskog pritiska tokom VTK) 3, sveže zamrznuta plazma ili transfuzija pune krvi (radi održavanja nivoa prokoagulanata tokom VTK) i transfuzija resuspendovanih eritrocita ili pune krvi (u cilju održavanja nivoa hematokrita tokom VTK). Hemodilucija pozitivno utiče na viskoznost krvi tokom održavanja hipotermije, ali ima i svoje neželjene efekte, kao što su: nastanak anemije (sa smanjenim kapacitetom krvi za prenos kiseonika), smanjenje nivoa plazma proteina i faktora koagulacije (što doprinosi nastanku tkivnog edema i koagulopatije), poremećaj elektrolitne Tabela 2.Razlike između adultnog ili pedijatrijskog vantelesnog krvotoka VTK=vantelesni krvotok Parametar Adultni bolesnik Pedijatrijski bolesnik Procenjena zapremina krvi 65 ml/kg <10kg:85 ml/kg (285 ml/3 kg) (4-5 l na 70 kg) Dilucioni efekat na zapreminu krvi 25-33% % Dodatak pune krvi ili resuspendovanih Retko Uobičajeno eritrocita prajmingu Potrošnja kiseonika 2-3 ml/kg/min 6-8 ml/kg/min Pun protok VTK na 37⁰C ml/kg/min ml/kg/min za<3kg Minimalna temperature VTK Retko < C Uobičajeno C Primena totalnog cirkulatornog aresta Retka Uobičajeno ili VTK sa malim protokom Perfuzioni pritisak mmhg mmhg Acido-bazni menadžment Uglavnom Alfa-stat Alfa-stat i/ili ph-stat Regulacija glikemije Hipoglikemija Hiperglikemija Retko (hepatička lezija) Često, leči se insulinom Često; redukovani depoi Retko; rizik-rebound hipoglikemija

4 258 SJAIT 2012/3-4 ravnoteže i naglašeno oslobađanje stres hormona i aktivacija sistema komplementa. 2,4 2. Optimalni hematokrit tokom vantelesnog krvotoka Kao i kod odraslih bolesnika, još uvek postoje kontroverze o optimalnom nivou hematokrita (Hct) tokom VTK. U većini centara se održava Hct oko 20±2, a pad vrednosti ispod 18 je indikacija za primenu transfuzije1.uobičajeno se kod dece na osnovu očekivane i željene vrednosti Hct tokom VTK (izračunate pomoću specijalne formule1) donese odluka o eventualnoj primeni transfuzije u sam prajming pre početka VTK. 3. ph menadžment Dva pristupa se koriste u održavanju acido-bazne ravnoteže i parcijalnog pritiska ugljen dioksida (pco2) tokom VTK: ph-stat i alfa-stat pristup. Tokom hipotermije, solubilnost CO2 u krvi se povećava, tako da za datu koncentraciju CO2 u krvi, pco2 se smanjuje i nastaje alkalemija.u ph-stat pristupu u cilju kompenzacije povećane solubilnosti CO2 u hipotermiji, CO2 se dodaje mešavini gasova u oksigenatoru u cilju održavanja ph na nivou 7.40 i pco2 na 40 mmhg. Kada se krvni uzorak zagreje do sobne temperature, u gasnim analizama postoji hiperkapnija i acidoza. U alfa-stat metodu tokom hlađenja dozvoljava se da se ph poveća, što dovodi do nastanka hipokapnije i alkalemije in vivo. U krvnom uzorku zagrejanom do sobne temperature ph je 7.4 i pco2 40 mmhg. U poređenju sa adultnom populacijom, ph-stat pristup je, i pored intracelularne acidoze i enzimske disfunkcije, povezan sa boljim neurološkim ishodom, ubrzanim oporavkom elektroencefalograma i smanjenim brojem postoperativnih konvulzija u pedijatrijskoj populaciji. Primenom ph-stat pristupa cerebralni krvni protok (CKP) tokom reperfuzije se povećava, što stvara rizik nastanka novih embolijskih događaja i reperfuzione lezije. S obzirom da su cerebralne lezije kod odraslih najčešće povezane sa mikroembolizacijama, ph-stat pristup se retko koristi u adultnoj kardiohirurgiji. U pedijatrijskih bolesnika mikroembolizacije su izuzetno retke, a neuroni pokazuju veću osetljivost na ishemiju, zbog čega je izuzetno značajno da se održi i poboljša CKP tokom i posle hipotermije. Primenom alfastat pristupa, održava se autoregulacija cerebralnog krvnog protoka.u pedijatrijskoj populaciji, kako bi se iskoristili pozitivni efekti ph-stat metoda na hlađenju, a eliminisali negativni efekti na enzimsku funkciju tokom zagrevanja, česta je sukcesivna upotreba ph-stat i alfa-stat pristupa. 4. Sistemski inflamatorni odgovor Vantelesni krvotok je dobro poznati pokretač ekstenzivne inflamatorne reakcije, posebno u neonatusa i infant, u kojih se koriste relativno veliki sistemi za VTK i veći protok u odnosu na telesnu težinu bolesnika, kao i velika zapremina prajminga u odnosu na zapreminu cirkulišuće krvi, što doprinosi većoj izloženosti krvnih elemenata na endotelizovanoj stranoj površini. Nezreli i organski sistemi u razvoju pokazuju veću osetljivost na inflamatorno oštećenje, u poređenju sa adultnom populacijom. Savremena antiinflamatorna strategija obuhvata primenu steroida, inhibitora serinproteaza, modifikovanu ultrafiltraciju i heparinom obložen sistem 2,5. U okviru odgovora organizma na stres na VTK može se javiti hiperglikemia, koja je udružena sa značajnim povećanjem postoperativnog morbiditeta i mortaliteta kod odraslih, dok se kod dece morbiditet povećava ili ostaje nepromenjen 6,7. Kod dece se, za razliku od odraslih, mnogo češće od hiperglikemije javlja hipoglikemija. Deca imaju manje depoe glikogena jer jetra ima manji kapacitet i sposobnost za glikoneogenezu. Takođe, u bolesnika sa kongenitalnim srčanim oboljenjima, zbog poremećaja heptičke perfuzije, hepatička funkcija je kompromitovana, što doprinosi hipoglikemiji. Iz svega proizilazi značaj monitoringa glikemije tokom VTK i rapidna korekcija hipoglikemije primenom koncentrovane glukoze, kako bi se smanjio morbiditet u pedijatijskoj srčanoj hirurgiji. Neurološke posledice hipoglikemije su pogoršane hipotermijom i drugim faktorima koji modifikuju cerebralni protok Hipotermija Primena hipotermije tokom VTK ima značajne korisne efekte. Hipotermija smanjuje metabolizam i potrošnju kiseonika u tkivima i štiti ih od oštećenja u uslovima smanjenog krvnog protoka. Hipotermija doprinosi smanjenju inflamatornog odgovora na VTK i pruža mogućnost smanjenja protoka tokom VTK, čime se smanjuje plućni venski i kolateralni protok do srca i poboljšava ekspozicija operativnog polja. U kongenitalnoj srčanoj hirurgiji se koriste umereno hipotermični VTK, duboki hipotermični VTK sa niskim protokom i duboki hipotermični cirkulatorni arest. 1,9 Umereno hipotermični VTK (25-32ºC), koji se uobičajeno koristi kod odraslih kardiohirurških bolesnika, koristi se kod veće dece i adolescenata kod kojih postoji mogućnost za bikavalnu

5 VTK TOKOM KARDIOHIRURŠKIH PROCEDURA KOD DECE I ODRASLIH kanulaciju, kojom se smanjuje vraćanje krvi u desnu pretkomoru i omogućava se hirurška vizuelizacija operativnog polja 1. U neonatusa i infanta rigiditet kanila i kolapsibilnost gornje i donje šuplje vene može dovesti do opstrukcije vena i poremećaja venske drenaže iz mezenterične i cerebralne cirkulacije, zbog čega je bikavalna kanulacija tehnički teže izvodljiva i ređe se koristi. Duboki hipotermični VTK sa niskim protokom (50ml/kg/min) se koristi tokom kompleksnih kardiohirurških procedura radi obezbeđenja skoro bezkrvnog operativnog polja. Duboki hipotermični cirkulatorni arest, tokom najpreciznijih hirurških rekonstrukcija, obezbeđuje odličnu hiruršku ekspoziciju, eliminišući potrebu za nekoliko kanila u hirurškom polju i obezbeđujući mirno i potpuno bezkrvno operativno polje Ultrafiltracija Novorođenčad i infanti često imaju tendenciju da akumuliraju veliku količinu tečnosti tokom VTK, što dovodi do nastanka intersticijalnog edema celog tela sa plućnom i miokardnom disfunkcijom. Često, sternum mora da ostane otvoren nekoliko dana posle operacije. U cilju smanjenja tog problema koristi se nekoliko ultrafiltracionih tehnika: I. konvencionalna ultrafiltracija (tokom trajanja VTK ili kada je u venskom rezervoaru dovoljna zapremina tečnosti da se uradi filtracija), II. diluciona ultrafiltracija (efektivnau uklanjanju inflamatornih medijatora, a zasniva se na zameni volumena ultrafiltrata sa jednakom zapreminom kristaloidnog rastvora) i Zaključak III. modifikovana ultrafiltracija koja se koristi posle odvajanja od VTK, a pre primene protamina (ultrafiltrat se menja krvlju iz sistema, sa naglašenim hemokoncentracijskim efektom). Hemostaza i antikoagulantna terapija Postoperativna dranaža u pedijatriskoj kardiohirurgiji je značajniji problem nego u adultnoj kardiohirurgiji 10, iz nekoliko razloga: a) antiinflamatorni odgovor na VTK (aktivacija i deplecija trombocita i aktivacija komplementa sa poremećajem hemostaze) je naglašeniji u pedijatriskoj kardiohirgiji i inverzno je povezan sa starošću bolesnika. b) u odnosu na adultnu populaciju, u novorođenčadi i infanta se češće izvode složene i ekstenzivnije operacije sa mnogo većom rekon- 259 strukcijom i više suturnih linija, što stvara mnogo veću ranjivu hiruršku površinu koja je potencijalni izvor krvarenja. c) nezreo koagulacioni sistem u neonatusa, smanjena produkcija faktora koagulacije u jetri i povećana fibrinoliza doprinose postoperativnom krvarenju. d) bolesnici sa cijanogenim srčanim manama pokazuju veću tendenciju ka krvarenju u period pre i posle VTK. U pedijatrijskoj kardiohirurgiji se, kao i kod odraslih, pre započinjanja VTK primenjuje heparin (bazirano na telesnoj težini) u cilju postizanja ACT vrednosti preko 480 sec. Uobičajena doza heparina kod odraslih je U/kg. Kod infanta postoji povećana osetljivost na heparin koja se polako smanjuje od prve nedelje života do treće godine, kada se vrednost približava onoj observiranoj kod odraslih. Uobičajeno se primenjuje heparin u dozi od 200 U/kg, uz dodatnu dozu 1-3 U/ml u prajming, uz obavezno uzimanje u obzir sastava i zapremine prajminga u sistemu za VTK, posebno ako se sveža zamrznuta plazma dodaje prajmingu. U neonatusa se, zbog organske nezrelosti i predominantno upotrebe hipotermnog cirkulatornog aresta, značajno smanjuje metabolizam i ekskrecija heparina, zbog čega se primenjuje veća doza protamina za reverziju efekta heparina (4 mg/kg), u poređenju sa adolescenatima i odraslim bolesnicima (2 mg/kg). Mada globalno posmatrano sličan, sistem za vantelesni krvotok u dece je značajno različit od onog u adultnoj populaciji. Savremeni pristup pedijatrijskoj kardioanesteziji podrazumeva takozvanu minijaturizaciju sistema za VTK sa smanjenjem zapremine oksigenatora, filtera, kanila i pumpe u cilju smanjenja hemodilucije i inflamatornog odgovora i primenu različitih antiinflamatornih metoda usmerenih na inhibiciju aktivacije komplementa i modulaciju inflamatorne genske ekspresije. Literatura 1. Greeley WJ, Steven JM, Nicolson SC, Kern FH. Anesthesia for Pediatric Cardiac Surgery. In: Miller RD, editor Anesthesia, 5-th ed. New York: Churchill Levingston; 2000.p

6 Schure AY. Cardiopulmonary bypass in infants and children: what s new?s Afr J AnaesthesiolAnalg 2010;16(1): Marelli D, Paul A, Samson CP et al. Does the addition of albumin to the prime solution in cardiopulmonary bypass affect clinicaloutcome? J ThoracCardiovascSurg 1989; 98: Shen I, Giacomuzzi C, Ungerleider RM, et al. Current strategies for optimizing the use of cardiopulmonary bypass in neonates and infants. Ann ThoracSurg 2003;75:S Hickey E, Karamlou T, You J, Ungerleider RM. Effects of circuit miniaturization in reducing inflammatory response to infant cardiopulmonary bypass by elimination of allogeneic bloodproducts. Ann ThoracSurg 2006;81:S Yates AR, Dyke PC 2nd, Taeed R, et al. Hyperglycemia is a marker for poor outcome in the postoperative pediatric cardiac patient. PediatrCrit Care Med. Jul 2006;7(4): Wypij D, Newburger JW, Rappaport LA, et al. The effect of duration of deep hypothermic circulatory arrest in infant heart surgery on late neurodevelopment: the Boston Circulatory Arrest Trial. J ThoracCardiovasc Surg. Nov 2003;126(5): Caputo M, Bays S, Rogers CA, Pawade A, Parry AJ, Suleiman S, Angelini GD. Randomized Comparison Between Normothermic and Hypothermic Cardiopulmonary Bypass in Pediatric Open-Heart Surgery Ann ThoracSurg 2005;80: Murphy GS, HesselIIn EA, Groom RC. Optimal perfusion during cardiopulmonary bypass: an evidence-based approach AnesthAnalg 2009;108: Manno CS, Hedberg KW, Kim HC et al: Comparison of the hemostatic effects of fresh whole blood, stored whole blood, andcomponents after open heart surgery in children. Blood 1991; 77: Williams GD, Ramamoorthy C. Brain monitoring and protection during pediatric cardiac anesthesia. SemCardiothoracVascAnesth 2007;11: SJAIT 2012/3-4

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