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Terapia de repletie volemicaIoana Grintescu, Raluca Ungureanu, Liliana MireaClinica de Terapie IntensivaSpitalul Clinic de Urgenta Bucuresti
Distributia fluidelor in organism
Compozitie osmotica
Transport fluidePresiune hidrostatica si osmotica
Transport fluideExtravazare fluid la nivel capilar arterial prin pres. hidrostatica
Revenire fluid plasmatic la nivel capilar venos prin pres. coloid osmotica
Deplasare fluid in capilar limfatic prin pres. hidrostatica interstitiala
Echilibru intre fluid interstitial si intracelular/transcelularPosm plasma=2x[Na] + gluc/18 + uree/2,8 = 290 mosm/kg
Transport transcapilarForta Starling de filtrareKf [(Pc-Pi)- (pc-pi)] Kf: coeficient de filtrare a peretelui capilar Pc: presiune hidrostatica capilara pc: presiune oncotica plasmatica Pi: presiune hidrostatica interstitiala pi: presiune oncotica interstitiala : coefficient de rflexionTransport transcelularSchimb osmotic intra-extracelularCanale transmembranare pt apa - aquaporine
Definitia hipovolemiei
Absoluta (pierdere acuta de sange, aport insuficient)Relativa (vasodilatatie, leakage capilar crescut - sepsis)
Cand exista discrepanta intre volumul sangvin circulant efectiv si capacitanta vaselor sangvine deficit de volum > 20% - semne clinicedeficit de volum > 40% - prognostic fatal frecvent
Hipovolemia - etiologieTrauma - volum sangvin circulant prin hemoragie (>20%)
Deshidratarea pierderi digestive (diaree, varsaturi)
Sepsis - RVP, disfunctie endoteliala, pierderi in spatiul trei
Hipovolemia - consecinteProportional cu pierderea volum sangvinActivare neuromormonala- flux fluidic fiziologic endogenSNS vasoconstrictie, FC, contractilitate miocardSist. renina AT-aldosteron vasoconstrictie, reabsorbtie renala Na, apaMetabolic lipoliza, gluconeogeneza cu hiperglicemie (hiperosmolaritate cu migrare apa din interstitiu)Flux intravascular de fluid din sp. Interstitial si intracelular
Leziune traumatica cu SIRS, alterare endoteliala eflux fluid din vas in interstitiu (pierderi spatiul trei)
ischemie tisularaMODS / MSOFintestine,rinichieliberareendotoxinesocsepticvasoconstrictieperfuzie inadecvataflux capilar inadecvatvolum sanguin redusdebit cardiac redus DO2 redusalterare hemodinamicaImportanta combaterii hipovolemieihipovolemiesi soc
Obiectivele resuscitariiPVC=15 mmHgPcwp (wedge pressure) =10-12 mmHgCardiac Index >3 L/min/m2VO2 >100 ml/min/m2Lactat < 4 mmol/LBeficit baze 3.+3 mmol/LParametrii dinamici de raspuns la umplere volemica
Cu ce?Substituenti de plasma:Solutii cristaloide: NaCl 0,9%, sol. Ringer etc.Solutii coloidale: cresc presiunea coloid osmoticaSange si produse derivate: MER, PPC, trombocite
Solutii cristaloide
Solutie ideala?
Compozitia plasmeimOsm/l H2ONa+142K+4,2Ca++1,3Mg++0,8Cl-108HCO3-24HPO4-, H2PO4-2SO4-0,5Aminoacizi2Creatina0,2Lactat1,2Glucoza5,6Proteina1,2Uree4Altele4,8Total mOsm/l301,8Activitate osmolara corectata282Presiunea osmotica totala 37oC (mmHg)5443
Solutii cristaloide balansate
Solutia NaCl 0,9% ?Dezavantajehipertonie (Osm 308)nu contine alti electrolitinu contine sisteme tamponcontinut excesiv de Cl- 154 mEq/L (95-105 mEq/L in plasma)
Acidoza metabolica indusa de NaCl in exceshipernatremiehipercloremie
Serul fiziologic (NaCl 0,9%) nu este fiziologic
Solutii cristaloide balansate
Krll et al., 19930200400600800100012001400sfarsitul perfuziei30 min60 min120 min[ml]Efectul volemic al diferitelor solutii perfuzabile (500 ml)Ringer lactatRemanenta intravasculara
Cresterea in volum (ml) dupa infuzia a de 1000 ml(Lampe colab., 1976)Efectul volemic al diferitelor solutii perfuzabiledupa 90 minute
0102030405060708090Haljame 2000%Distributia relativala 30 min 1 h de la perfuzie
Limitele resuscitarii volemice cu cristaloiziBaron J.- Crystalloids versus colloid in the treatement of hypovolemic shock 2000
InterstitiunormalInterstitiusoc resuscitare cu cristaloizihematiiJ. Boldt 2004Disfunctia microcirculatorie
Edeme perifericeResuscitarea eficienta ar producemonstruozitati+/- Edem pulmonar
** Tommasino 1988 6% HES RL control012345Hemodilutietimp (ore)PIC (mmHg) Edem cerebral
Sindromul de compartiment abdominalapare la pacientii cu soc severdupa resuscitare masiva cu cristaloiziedem masiv a mucoasei digestiveedem ale peritoneului si mezenterului
reprezinta un cerc vicios de agravare spre MODS / MSOFTHE LANCET, 2004; 363: 1988-96The next generation in shock resuscitationFrederick A Moore, Bruce A McKinley, Ernest E Moore
Controlul glicemieiLactatul glucoza in ficatM.James TATM 2005
Dificultati in controlul glicemiei la pacientii diabetici
Pacientul critic ? In contextul mentinerii euglicemiei vezi Van den Berghe
cristaloizihipercoagulabilitateCoagulareStatus hipercoagulant:balanta inclinata datorita reducerii activitatii ATIIIRuttmann si colab. 2002. BJ Anaesthesia 89 Ruttmannn si colab 2001Anaesthesia Intensive Care Hipercoagulabilitatea pare sa fie independenta de tipul de cristaloid folositBoldt J Anaesthesia Analgesia 94 2002
Solutii hipertoneSolutii NaCl 3 7,5%
Solutii amestec cristaloizi-coloiziHyperhaesElectroliti 7,2% NaCl (1232 mmol/l Na)Osmolaritate calculata 2464 mmOsm/lGreutate moleculara medie (kDa) 200HAES 200 6%
Solutii hipertoneIndicatii resusucitare eficiente cu volume mici (prespital)soc hipovolemic refractartraumatisme craniene
EfecteMobilizarea apei extravasculara Ameliorarea microcirculatiei cresterea perfuziei tisularaEfect vasodilatator direct (sistemic si pulmonar)Efect inotrop pozitiv direct
Solutii coloidaleTipuri de coloiziNaturali albuminaPPC
ArtificialigelatinedextraniHES
Albumina
Albumina66 kDa, 75% din PCO a plasmei5% - izoosmotica (PCO 20 mmHg)20% - hiperosmotica (PCO 80-100 mmHg)
Hipoalbuminemie in sepsis prin cresterea volumului de distributie si extravazare prin leakage capilar
2 meta-analize- pacient critic Cochrane Injuries Group Albumin Reviewers. BMJ 1998; 317: 235-240.Wilkes MM, Navickis RJ. Ann Intern Med 2001; 135; 149-164.
RezultateStudiul SAFE (NEJM 2004)Saline versus Albumin Fluid Evaluation studystudiu multicentric, randomizat, dublu orbpacienti critici, cu diverse patologii~ 43% chirurgicali~ 47% medicali6997 pacienti4% albumin: 3.497 pacientiSF: 3.500 pacienti
Finfer S et al. NEJM, 2004mesajul studiului: utilizarea albuminei este greu de justificat, nefiind superioara SF
Polipeptide extrase din colagen de origine animala ( os, sinoviale etc) Masa moleculara= 30 35 KDConcentratie = 3.0% - 5.5%, hipoosmoticeEliminare renala rapidaEfect de volum 70%Reactii alergice- eliberare de histamina stabilitate redusa (precipita la temperaturi scazute)GelatineFDA a retras de pe piata gelatina in anul 1976 datorita profilului de siguranta scazut
Dextranipolizaharide (origine bacteriana) 10% D 40 (40 kDa) hiperosmotic (200% efect de volum)6% D 70 (70 kDa) isoosmotic (100% efect de volum)interfera cu coagularea, risc de sangerareReactii anafilactice foarte frecventeBaron JF Yearbook of Intensive Care and Emergency Medicine. Berlin, Germany: Springer, 2000:443-466.
HES (Hydroxy Ethyl Starch)
Amilopectina din porumb (> 95%)
Gelatins, U. Bornemann
CaracteristiciExista diferente importante, ce influenteaza farmacodinamica
masa moleculara gradul de substitutie pattern- ul de substitutie (raportul C2/C6)HES (Hydroxy Ethyl Starch)
Masa molecularaPragul renal: GM ~ < 60 70,000 D60 70,000200,000Masa molecularaHES (Hydroxy Ethyl Starch)
Degradare enzimatica via -1,4-amilazaMetabolizarea este influentata de:
1. Gradul de substitutie(mare: intarzie degradarea)2. pattern de substitutie(mare: intarzie degradarea) C2/C6
3. Masa moleculara ( doar la valori < 70.000D prag renal) 61,4-bindingCH2-CH2OH411 1,6-bindingCH2-CH2OHCH2-CH2OHCH2-CH2OHCH2-CH2OHHES (Hydroxy Ethyl Starch)
Caracteristici10% HES 6% HES 6% HES3% HES6% HES200/0.5200/0.5130/0.4200/0.570(40)/0.5
Efect de volum:*~ 145%~ 100%~ 100%~ 60%~ 70 90%
Durata:*~ 3 4 h~ 3 4 h~ 3 4 h~ 1 2 h~ 1 2 h
T1/2 plasmatic:~ 3 4 h~ 3 h~ 3 h~ 2 3 h~ 2 3 h
Doza maxima:20 ml33 ml50 ml**66 ml20 ml(ml/kg/zi)
Hematocrit:
Vascozitate plasmatica
Indicatii:repletie volemica repletie volemica repletie volemica repletie volemicarepletie volemicaSTI, traumachirurgie electiva UPU, STI, trauma pe termen scurt pe termen scurt
necesar sg necesar sg necesar sg *15 min / 500 ml, **temporr
HES (Hydroxy Ethyl Starch)
Diferente intre solutiile de coloiziColoidGMGSC2:C6 Durata efectului
Haemaccel35kD--1-2hGelofusine30kD--2-4hVoluven130kD0.42-3hHAESteril200kD0.453-4hHemohes200kD0.5 4-5hEloHAES200kD0.6 5-6hHespan450kD0.7 5-6h
Reactii alergiceStudiu prospectiv, multicentric (~ 20.000 p)Laxenaire si colaboratorii (1994)%0.345%0.273%0.099%
0.058%Reactii adverse ale coloizilor
timpului de sangerareJakobson (1995), Evans (1996), Jonge (1998)
alterarea agregarii plachetareTabuchi (1995), Thurner (1995)Tigchelar (1997)*
alterarea formarii cheaguluiMardel (1996), Brodin (1985), Baddely (1996)
concentratiei plasmatice de Ca2+Evans (1997)
factor vW, ristocetin-cofactor Jonge (1998), Tigchelar (1997)** HES vs. Gelatina: rezultate mai bune pt. HES
Reactii adverse ale coloizilorInfluente asupra coagularii
Reactii adverse ale coloizilor( HES)Sunt cu atat mai pronuntate cu cat masa moleculara si gradul de substitutie sunt mai mariReactii anafilactice (0,058%) de obicei de gradul I/IIPrurit in cazul administrarii de doze mari, pe perioade lungiAlterari ale coagularii prin scaderea nivelului de F VIII, vW; nu s- au evidentiat pt. HES cu GM micaDisfunctie renala inca in discutie
Coloidul idealNu se acumuleaza in tesuturiNu se acumuleaza in plasmaNu influenteaza hemostazaNu influenteaza sistemul imunSteril Nu este antigenic
Nu are potential alergic Nu este proinflamator Nu este toxic, teratogen, mutagenNu influenteaza testele de diagnosticInterferenta redusa cu alte droguriToleranta buneEliminare completaNational Acad. Sci., USA 1963
Coloizi sau cristaloizi ?Efect plasma expanderAmelioreaz reologia i oxigenarea visceral Efect hipocoagulantEfecte adverseCost mai ridicatRemanenta intravasculara redusaMigreaz extracelularEfect hipercoagulantResuscitarea microcirculatorie inadecvataEfecte adverse minimeCost sczutCristaloiziColoizi
*A. Total body water makes up approximately 55 to 60% of body weight in adult males and somewhat less, perhaps 50 to 55%, in adult females (due to a higher proportion of body fat). Within both sexes there is considerable variability in water content, again presumably related mainly to differences in lean body mass. For a 70 Kg man, body water is around 42 L.B. Body water is divided into that located inside cells and that located outside cells. 1. Intracellular fluid. Approximately 36% of body weight. This is approximately 25 L in a 70 Kg man.2. Extracellular fluid. Approximately 24% of body weight. The two principal extracellular fluid compartments are plasma (blood minus the red and white cells) and the interstitial space (the space between the cells that makes up organs). In addition, there is extracellular water located in bone and dense connective tissue, and transcellular water in secretions such as digestive secretions, intraocular fluid, cerebrospinal fluid, sweat, and synovial fluid.a) A typical extracellular volume is about 17 L.b) Plasma. A 70 Kg man has a plasma volume of about 3 L which is about 4.5% of body weight.c) Interstitial space. The interstitial space is about 8 L in a 70 Kg man. This is 11.5% of body weight.d) The remaining 6 L of extracellular fluid is located in the minor compartments.
*A. Plasma water is the initial body access point for ingested nutrients, and the exit point for the bodys waste products. Access to all cells of the body except the red cells is via the interstitial space.B. The ionic composition of extracellular and intracellular compartments is markedly different. However, the total osmotic concentrations of extracellular and intracellular fluids are similar (despite having slightly different total ionic concentrations).1. The principle extracellular cation is Na+. The principle extracellular anions are chloride and bicarbonate.2. The principle intracellular cation is K+. The principle intracellular anions are phosphates [both inorganic (HPO42-, H2PO4-) and organic (ATP, etc.)] and proteins.Water is the universal solvent Solutes are broadly classified into:Electrolytes inorganic salts, all acids andbases, and some proteinsNonelectrolytes examples include glucose,lipids, creatinine, and urea Electrolytes have greater osmotic power thannonelectrolytes Water moves according to osmotic gradients*Compartmental exchange is regulated by osmotic and hydrostatic pressuresNet leakage of fluid from the blood is picked up by lymphatic vessels and returned to theBloodstream Exchanges between interstitial and intracellular fluids are complex due to the selective permeability of the cellular membranes*Plasma is the only fluid that circulatesthroughout the body and links external andinternal environments Osmolalities of all body fluids are equal;changes in solute concentrations are quicklyfollowed by osmotic changes*******