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Terapia de repletie volemica
Ioana Grintescu, Raluca Ungureanu, Liliana Mirea Clinica de Terapie Intensiva Spitalul Clinic de Urgenta Bucuresti
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Distributia fluidelor in organism
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.
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Compozitie osmotica A. Plasma water is the initial body access point for ingested nutrients, and the exit point for the body’s 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 and bases, and some proteins Nonelectrolytes – examples include glucose, lipids, creatinine, and urea Electrolytes have greater osmotic power than nonelectrolytes Water moves according to osmotic gradients
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Transport fluide Presiune hidrostatica si osmotica
Compartmental exchange is regulated by osmotic and hydrostatic pressures Net leakage of fluid from the blood is picked up by lymphatic vessels and returned to the Bloodstream Exchanges between interstitial and intracellular fluids are complex due to the selective permeability of the cellular membranes
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Transport fluide Posm plasma=2x[Na] + gluc/18 + uree/2,8 = 290 mosm/kg
Extravazare 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/transcelular Plasma is the only fluid that circulates throughout the body and links external and internal environments Osmolalities of all body fluids are equal; changes in solute concentrations are quickly followed by osmotic changes Posm plasma=2x[Na] + gluc/18 + uree/2,8 = 290 mosm/kg
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Transport transcapilar
Forta Starling de filtrare Kf [(Pc-Pi)-σ (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 σ : coefficient de réflexion Transport transcelular Schimb osmotic intra-extracelular Canale transmembranare pt apa - aquaporine
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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 clinice deficit de volum > 40% - prognostic fatal frecvent
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Hipovolemia - etiologie
Trauma - volum sangvin circulant prin hemoragie (>20%) Deshidratarea – pierderi digestive (diaree, varsaturi) Sepsis - RVP, disfunctie endoteliala, pierderi in “spatiul trei”
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Hipovolemia - consecinte
Proportional cu pierderea volum sangvin Activare neuromormonala- flux fluidic fiziologic endogen SNS – vasoconstrictie, FC, contractilitate miocard Sist. renina –AT-aldosteron – vasoconstrictie, reabsorbtie renala Na, apa Metabolic – 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”)
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Importanta combaterii hipovolemiei
si soc soc septic eliberare endotoxine volum sanguin redus debit cardiac redus DO2 redus alterare hemodinamica intestine, rinichi MODS / MSOF vasoconstrictie perfuzie inadecvata flux capilar inadecvat ischemie tisulara
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Obiectivele resuscitarii
PVC=15 mmHg Pcwp (wedge pressure) =10-12 mmHg Cardiac Index >3 L/min/m2 VO2 >100 ml/min/m2 Lactat < 4 mmol/L Beficit baze –3….+3 mmol/L Parametrii dinamici de raspuns la umplere volemica Cu ce? Substituenti de plasma: Solutii cristaloide: NaCl 0,9%, sol. Ringer etc. Solutii coloidale: cresc presiunea coloid osmotica Sange si produse derivate: MER, PPC, trombocite
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Solutii cristaloide
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Solutie ideala? Compozitia plasmei mOsm/l H2O Na+ 142 K+ 4,2 Ca++ 1,3
Mg++ 0,8 Cl- 108 HCO3- 24 HPO4-, H2PO4- 2 SO4- 0,5 Aminoacizi Creatina 0,2 Lactat 1,2 Glucoza 5,6 Proteina Uree 4 Altele 4,8 Total mOsm/l 301,8 Activitate osmolara corectata 282 Presiunea osmotica totala 37oC (mmHg) 5443
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Solutii cristaloide balansate
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Solutia NaCl 0,9% ? Serul fiziologic (NaCl 0,9%) nu este fiziologic
Dezavantaje hipertonie (Osm 308) nu contine alti electroliti nu contine sisteme tampon continut excesiv de Cl- 154 mEq/L ( mEq/L in plasma) Acidoza metabolica indusa de NaCl in exces hipernatremie hipercloremie
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Solutii cristaloide balansate
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Solutii cristaloide Avantaje: Dezavantaje: Reactii adverse minime
Cost scazut Utile in hipovolemia usoara-moderata: Raport 1:3 pierderi sg: necesar sol cristaloide Remanenta vasculara scazuta <1 h. (migreaza extravascular) Mai acentuata in caz d epermeabilitate vasculara crescuta sau disfunctie endoteliala Efect volemic f redus Dezavantaje: Acidoza hipercloremica (pt SF) Induc edeme in caz de resuscitare masiva
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Remanenta intravasculara
Efectul volemic al diferitelor solutii perfuzabile (500 ml) Kröll et al., 1993 1400 [ml] 1200 1000 800 600 400 200 sfarsitul perfuziei 30 min 60 min 120 min Ringer lactat GEL 3.5% 10% HES 200/0,5 HES 6% 200/0.5 HES 6% 200/0.6
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Efectul volemic al diferitelor solutii perfuzabile
Cresterea in volum (ml) dupa infuzia a de 1000 ml 100 200 300 400 500 600 700 800 900 1000 6% HES 450/0.7 5% Albumine Haemaccel NaCl 710 490 240 180 (Lampe colab., 1976) dupa 90 minute
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Distributia relativa la 30 min – 1 h de la perfuzie Haljamäe 2000
permeabilitate capilara crescuta + disfunctie endoteliala Cristaloid HES 85-90% 10-15% 40-50% 50-60% permeabilitate capilara normala Cristaloid HES 80% 20% 30% 70% permeabilitate capilara crescuta Cristaloid HES 80-85% 15-20% 30-40% 60-70% % 90 80 70 60 50 40 30 20 10 Extravascular Intravascular Haljamäe 2000
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Limitele resuscitarii volemice cu cristaloizi
Baron J.- “Crystalloids versus colloid in the treatement of hypovolemic shock” 2000
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Disfunctia microcirculatorie
J. Boldt 2004 normal soc – resuscitare cu cristaloizi flux sanguin hematii celule endoteliale Interstitiu Interstitiu
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Edeme periferice +/- Edem pulmonar Resuscitarea eficienta ar produce
monstruozitati
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Edem cerebral * * -1 1 2 3 4 5 6 7 PIC (mmHg) 6% HES RL control 1 2 3
1 2 3 4 5 6 7 PIC (mmHg) 6% HES * RL control * x ± SD * p < 0,05 1 2 3 4 5 timp (ore) Hemodilutie Tommasino 1988
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Sindromul de compartiment abdominal
apare la pacientii cu soc sever dupa resuscitare masiva cu cristaloizi edem masiv a mucoasei digestive edem ale peritoneului si mezenterului reprezinta un cerc vicios de agravare spre MODS / MSOF THE LANCET, 2004; 363: The next generation in shock resuscitation Frederick A Moore, Bruce A McKinley, Ernest E Moore
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Controlul glicemiei Lactatul glucoza in ficat
M.James TATM 2005 Dificultati in controlul glicemiei la pacientii diabetici Pacientul critic ? In contextul mentinerii euglicemiei vezi Van den Berghe
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hipercoagulabilitate
Coagulare cristaloizi hipercoagulabilitate Status hipercoagulant: balanta inclinata datorita reducerii activitatii ATIII Ruttmann si colab BJ Anaesthesia 89 Ruttmannn si colab 2001Anaesthesia Intensive Care Hipercoagulabilitatea pare sa fie independenta de tipul de cristaloid folosit Boldt J Anaesthesia Analgesia
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Solutii hipertone Solutii NaCl 3 – 7,5%
Solutii amestec cristaloizi-coloizi Hyperhaes Electroliti 7,2% NaCl (1232 mmol/l Na) Osmolaritate calculata 2464 mmOsm/l Greutate moleculara medie (kDa) 200 HAES 200 6%
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Solutii hipertone Indicatii Efecte
resusucitare eficiente cu volume mici (prespital) soc hipovolemic refractar traumatisme craniene Efecte Mobilizarea apei extravasculara Ameliorarea microcirculatiei cresterea perfuziei tisulara Efect vasodilatator direct (sistemic si pulmonar) Efect inotrop pozitiv direct
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Solutii coloidale Tipuri de coloizi
Naturali albumina PPC Artificiali gelatine dextrani HES
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Albumina
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Albumina 66 kDa, 75% din PCO a plasmei 5% - izoosmotica (PCO 20 mmHg)
20% - hiperosmotica (PCO 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: Wilkes MM, Navickis RJ. Ann Intern Med 2001; 135;
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Studiul SAFE (NEJM 2004) Saline versus Albumin Fluid Evaluation study
Finfer S et al. NEJM, 2004 Rezultate studiu multicentric, randomizat, dublu orb pacienti critici, cu diverse patologii ~ 43% chirurgicali ~ 47% medicali 6997 pacienti 4% albumin: pacienti SF: pacienti mesajul studiului: utilizarea albuminei este greu de justificat, nefiind superioara SF
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Gelatine Polipeptide extrase din colagen de origine animala ( os, sinoviale etc) Masa moleculara= 30 – 35 KD Concentratie = 3.0% - 5.5%, hipoosmotice Eliminare renala rapida Efect de volum 70% Reactii alergice- eliberare de histamina stabilitate redusa (precipita la temperaturi scazute) FDA a retras de pe piata gelatina in anul 1976 datorita profilului de siguranta scazut
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Dextrani polizaharide (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 sangerare Reactii anafilactice foarte frecvente Baron JF Yearbook of Intensive Care and Emergency Medicine. Berlin, Germany: Springer, 2000:
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HES (Hydroxy Ethyl Starch)
Caracteristici Exista diferente importante, ce influenteaza farmacodinamica masa moleculara gradul de substitutie pattern- ul de substitutie (raportul C2/C6) De ce substitutie? Creste capacitatea de legare a moleculelor de apa Intarzie degradarea enzimatica
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HES (Hydroxy Ethyl Starch)
Caracteristici 10% HES 6% HES 6% HES 3% HES 6% HES 200/ / / /0.5 70(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 ml 33 ml 50 ml** 66 ml 20 ml (ml/kg/zi) Hematocrit: Vascozitate plasmatica Indicatii: repletie volemica repletie volemica repletie volemica repletie volemica repletie volemica STI, trauma chirurgie electiva UPU, STI, trauma pe termen scurt pe termen scurt necesar sg necesar sg necesar sg *15 min / 500 ml, **temporär
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Laxenaire si colaboratorii (1994)
Reactii adverse ale coloizilor Reactii alergice % 0.345% 0.273% 0.099% 0.058% Studiu prospectiv, multicentric (~ p) Laxenaire si colaboratorii (1994)
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Reactii adverse ale coloizilor( HES)
Sunt cu atat mai pronuntate cu cat masa moleculara si gradul de substitutie sunt mai mari Reactii anafilactice (0,058%) de obicei de gradul I/II Prurit – in cazul administrarii de doze mari, pe perioade lungi Alterari ale coagularii prin scaderea nivelului de F VIII , vW; nu s- au evidentiat pt. HES cu GM mica Disfunctie renala – inca in discutie
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Coloidul ideal Nu se acumuleaza in tesuturi Nu se acumuleaza in plasma
Nu influenteaza hemostaza Nu influenteaza sistemul imun Steril Nu este antigenic Nu are potential alergic Nu este proinflamator Nu este toxic, teratogen, mutagen Nu influenteaza testele de diagnostic Interferenta redusa cu alte droguri Toleranta bune Eliminare completa National Acad. Sci., USA 1963
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Coloizi sau cristaloizi ?
Remanenta intravasculara redusa Migrează extracelular Efect hipercoagulant Resuscitarea microcirculatorie inadecvata Efecte adverse minime Cost scăzut Efect plasma expander Ameliorează reologia şi oxigenarea viscerală Efect hipocoagulant Efecte adverse Cost mai ridicat
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