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Colloid and Renal Function

Ike SR Anesthesiology/ICU RSHS/FKUP Bandung

Fluid therapy
Resuscitation goals adequate of microcirculation Maintenance fluid , electrolyte, acid base balance Nutrition energy metabolism and cell construction to maintan organ function

Life-Threatening Consequences of Inadequate Resuscitation

Lactic acidosis Acute renal failure Multisystem organ failure

Colloids or Crystalloids?
There are two main physiologic reasons to believe that colloid could be more efficacious than crystalloid: (1) more rapid plasma volume expansion, since the colloid solution remains in the vascular space (in contrast to saline, two-thirds of which enters the interstitium); (2) a lesser risk of pulmonary edema, since dilutional hypoalbuminemia will not occur .

Indication of colloid therapy


Fluid resuscitation intravascular resuscitation severe intravascular volume deficit Fluid resuscitation in severe hypoalbuminemia Usually used in conjunction with crystalloid if fluid load is very high Fluid boluses in critically ill patients, where volume is critical crystalloid used would be excessive : ICU patients, renal dysfunction/failure, pulmonary edema

Colloid
Intravascular space expander Volume expansion varies per-individual colloid chosen Osmotically active with high molecular weight Maintain oncotic pressure Influence coagulation system Variable electrolyte content Intra-vascular half-life varies between 2 8 hour Adverse reaction More expensive than crystalloids

Current available colloid solutions


Albumin Dextrans Hydroxyethyl starches Gelatin succinylated gelatin , polygelines All have their merits and area of usage clinically In Europe trend to use HES ( starches ) In USA crystalloids and gelatins not freely available

What is the ideal colloids ?


Rapidly replaces blood volume losses Restore the hemodynamic balance Normalizes microcirculatory flow Have sufficiently long intravenous life Improves hemorrheology Be readily metabolized, excreted, and well tolerated Be free of side effect anaphylactoid reaction, interfere the coagulation system Contribute to blood savings Cost effective

No colloid fits into all the criteria, all of the time

What is the idea ?

Use the best colloid for the selective patients to achieve the goals of therapy with the least of side effect

Albumin
One of the original plasma expander Accounts for 60 80 % of plasma oncotic pressure Derived from pooled human plasma Available as 5 % and 20% solution Blood albumin level prognostic indicator !, not an absolute value to be maintained by exogenous albumin infusion Blood derived product

Albumin ( cont )

Dextran
Branched chain polysacharide Produced plasma expansion by a colloidal osmotic effect Mostly used in restoring intravascular volume 2 preparation :
Dextran 70 Dextran 40

Both are in saline 0.9% 50- 70% excreted unchanged in the urine, the rest is metabolized in the liver H2O + CO2

Dextran ( cont ..)


Risk of bleeding Higher risk of anaphylactoid reactions Interfere blood typing Anti platelet in dehydration increase viscosity of fluid in renal tubule Can be associated with renal failure/ compromised

Gelatin
Second most commonly used plasma expander after hydroxyethyl-starch 2 different formulations
4% modified 9 succinylated fluid gelatin gelofusin 3.5% polygeline degraded gelatin polypeptides cross linked via urea bridges Haemaccel

Succinylated gelatin result in negative charge so spread out the molecule result in filling of iv volume and sealed endothelial leakage

Gelatin ( cont )
MW 30000-35000 dalton rapi excretion via urine with complete plasma clearance within 3 days, complete excretion from the body in 1 week Up to 50% removed within 1st 4-8 hour No storege in RES Claimed to be no effect on coaulation unless due to dilution No limitation of volume to be given Benefit over HES in renal compromised patients after renal transplant ( Cittanova M, lancet December 1996 ) Derived from animal bovine : theoretical risk of transmission of contagion

Gelatin ( cont)
Rapid migration out of the iv space needs more volume to achieve the same volume expansion effect of HES possibility of overhydration especially in critically ill/ renal/cardiac dysfunction Volume effect 3-4 hours Anaphylactoid reaction >>

Hydroxyethyl- starch
Derived from chemically modified amylopectin ( wax corn starch) Osmolarity 310 mOsm close to normal physiological osmolarity Concentration 6% and 10% Approximate pH 5.5 Available in saline 0,9% and in lactated ringer solution

Capillary Physiology

HES
MW vary 450 130 dalton Differ in degree of substitution substitution ratio Vary greatly in the t1/2 intravascularly, duration of effect and plateau effect and rate of elimination Plateau effect up to 4 hour, volume efficacy 1:1 duration varying 4-8 hour Broken down by amylase in the plasma Removed by renal excretion after degradation ( small molecule 50 ) Low incidence of anaphylactoid reaction More expensive crystalloid

Risk of anaphylactoid reactions with colloids


Reaction ( % of patients exposed )
0.35 0.3 0.25 0.2 0.15 0.1 0.05 0 1st Qtr Reaction (% of patients exposed) gelatin dextran albumin HES

HES ( cont..)
High molecular weight HES have a very narrow therapeutic benefit range Medium to lower MW HES more ideal as volume resuscitation Decrease the increase of vasoactive mediators & beneficially alter membrane stabilization Boldt M, Anest/analg 1996 showed improved systemic HD, splanchnic perfusion in trauma & septic patient Voght N, Anest-analg 1996 demonstrated the safety of HES 200/0.5 in doses larger than the recommended dose not for renal impairment

HES 130/0.4 (6% - Voluven) infusion during CVVH resulted in stable HD accompanied with constant value of diuresis and creatinin clearance and DO2 Histologic PA did not reveal significant increased cellular infiltration of alveolar capillaries compared to other colloids

Anesthesi Analg 2002, 95: 544-51

Severe Renal dysfunction

96h

72h
48h

0-24h

Conclusion of this study


HES 130/0.4 ( 500 cc 6%) can be administered to patients with severe renal impairment as long as urine flow is preserved No plasma accumulation in this study This study not perioperative and not ICU patients

Anesthesiology 2002; 970::460-70

Microcirculatory analysis : Arteriolar & venular diameter Functional Capillary Density Rolling leukocyte fraction in arteriole & venular Adherent leukocyte counts in arteriolar & venular

Arteriolar & venular vasodilatation

Arteriolar diameter
HES
Base line
33.7(9.9)

Venular diameter
HES NaCl Control
37.8(7.3) 37.4(5.4) 40.5(8.9) 37.9(4.6)

NaCl
38.8(15.3 ) )

Control

41.6(16.1) 32.9(5.2)

30 min

33.2(7.1) 41.2(17.1

40(18)

35.3(5)

3h
4h 8h 24h

32.7(8.5) 40.5(17.2
)

39.4(14.4) 37.6(5.3) 50.5(16.2) 42.6(8.5)


34.8(17.6) 36.8(4.9) 47.7(12.1) 34.7(12.6) 34.3(5.5) 40.6(18.7) 29.7(5.5) 43.2(9.5) 44.2(9.4)

31.9(9.6) 38.2(15.6
)

50.8(8) 40.5(7.3) 36.6(8.2)

31.1(8.9) 39.4(10)
32.8(13.9) 46.2(15.1 )

HES 130/0.4
Functional Capillary Density and macromolecular leakage caused by sepsis attenuated by HES 130/0.4 vs crystalloid and control

Rolling leukocyte HES 130/0.4 vs NaCl & Control

All groups decreased arteriolar and venular leukocyte rolling fraction at 30 min
Rolling leukocyte in arteriol Rolling leukocyte in venule

HES
Base line 30 min 3h

NaCl 3.0(1.5) 0.3(0.8) 3.0(6.9)


4.3(10.1)
39.4(29.3) 33.8(34.6)

Control 4.6(6.2) 0.0(0.0)


5.6(13.1)
54.3(41.7)
71.6(35.4)

HES
23.6(14.3)

NaCl
17.5(7.1)

Control 30.8(28) 5.1(7.4)


29.6(26.2)

0.3(0.4) 0.0(0.0) 2.0(3.4)

0.0(0.0)
39.7(33.6)

3.0(6.4)
24.3(26.7)

4h
8h 24 h

13(26.6)
39.4(43.1)

53.7(39.3)
84.5(20.7) 64.8(12.4)

20(21)
58.4(29.8) 72.8(26.1)

63(10.2)
73.8(19.5) 79.2(10)

1.0(2.0)

11.4(27)

Role of HES 130/0.4 inflammatory response


Decrease of leukocyte rolling inflammatory response ( early ) can be prevented attenuated the cascade process Renal function will be preserve by adequate microcirculation ( decrease micro-emboli formation )

Conclusion
How to choose the right colloid : Know the relevant benefit of each colloid give the colloid which achieve the maximal correction for the clinical deficit with the minimal volume given Choose the colloid with the least clinically proven side effect and complications Consider : anaphylactoid reaction, coagulation and renal function accumulation

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