1. Terapia de repletie volemica
Ioana Grintescu, Raluca Ungureanu, Liliana Mirea
Clinica de Terapie Intensiva
Spitalul Clinic de Urgenta Bucuresti

2. 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.

3. 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

4. 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

5. 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

6. 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

7. 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

8. Hipovolemia - etiologie
Trauma -  volum sangvin circulant prin hemoragie (>20%)
Deshidratarea – pierderi digestive (diaree, varsaturi)
Sepsis -  RVP, disfunctie endoteliala, pierderi in “spatiul trei”

9. 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”)

10. 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

11. 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

12. Solutii cristaloide

13. 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

14. Solutii cristaloide balansate

15. 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

16. Solutii cristaloide balansate

17. 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

18. 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

19. 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

20. 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

21. Limitele resuscitarii volemice cu cristaloizi
Baron J.- “Crystalloids versus colloid in the treatement of hypovolemic shock” 2000

22. Disfunctia microcirculatorie
J. Boldt 2004
normal
soc – resuscitare cu cristaloizi
flux sanguin
hematii
celule endoteliale
Interstitiu
Interstitiu

23. Edeme periferice +/- Edem pulmonar Resuscitarea eficienta ar produce
monstruozitati

24. Edem cerebral * * -1 1 2 3 4 5 6 7 PIC (mmHg) 6% HES RL control 1 2 31 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

25. 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

26. 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

27. 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

28. 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%

29. 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

30. Solutii coloidale Tipuri de coloizi
Naturali
albumina
PPC
Artificiali
gelatine
dextrani
HES

31. Albumina

32. 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;

33. 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

34. 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

35. 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:

37. 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

38. 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

39. 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)

40. 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

41. 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

42. 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