VOLUME THERAPY

Dr. Monish Raut Dept of Cardiac Anaesthesia Sir Ganga Ram Hospital New Delhi

Fluid Physiology
Total Body Water 0.6 L/kg
2/3 Intracellular (ICF) 1/3 Extracellular (ECF)

Cells 28

Litres

ICF Volume (0.4 L/kg) ECF Volume (0.2 L/kg)

Plasma Volume (0.05 L/kg) Interstitial Volume (0.15 /kg)

Interstitial fluid 10.5 Litres Blood volume 3.5 litres

Ratio of plasma volume to interstitial volume is 1-to-3 [rationale for 3-to-1

replacement of blood losses with crystalloid]

 Provide daily basal fluid requirements

Maintain or achieve normovolemia and haemodynamic stability Restitution of the fluid balance between the different fluid compartments Maintain adequate plasma COP Enhance microvascular blood flow Prevent/moderate cascade system activation and trauma induced increased blood coagulability Normalization of oxygen delivery to tissue cells and cellular metabolism Int J Intensive Care, 1999; 6: 20

Baillires Clin Anaesthesiol, 1997; 11: 49.

Clinical Situations Often Requiring customized Volume therapy

Management of patients with hemorrhage (e.g., GI bleed, ruptured AAA, cardiac redo cases , IVC tear, SVC tear ) Surgery, especially with large blood losses or large third space losses, such as liver transplantation or spinal correction surgery Management of burn patients Perioperative management of trauma patients Management of cardiopulmonary bypass Management of patients with sepsis syndrome
Complex situations: Acute Pancreatitis, DKA, Acute Renal Failure ALI/ ARDS

Features unique to Critical Illness

Critically ill patients do often have complex hemodynamics (hypovolemia, myocardial depression or both). Only in rare case does the diagnosis tell you what is the main physiological disturbance. Co-morbidities often complicate the hemodynamic status. Critically ill patients often present us with therapeutic conflicts (e.g., hemodynamic instability and ARDS).

Early Optimization of Hemodynamics improves outcome

Kern JW and Shoemaker WC Crit Care Med 30: 1686 1692, 2002

Metaanalysis of hemodynamic optimizaton in high risk patients

Rivers et al., N Engl J Med 345: 1368 1377, 2001

Early goal-directed therapy in the treatment of severe sepsis and septic shock

Goals of hemodynamic Management

Optimizing Stroke volume /Cardiac Output:
Measurement of SV/CO

Optimizing Preload:
Measurement of Preload Assessing Fluid Responsiveness

Avoiding Fluid Overload

Assessing Pulmonary Edema

Plasma Volume Expansion

Volume expansion is frequently used in critically ill patients to improve hemodynamics. Because of the positive relationship between ventricular end-diastolic volume and stroke volume, the expected hemodynamic response to volume expansion is an increase in right ventricular end-diastolic volume (RVEDV), left ventricular end-diastolic volume, stroke volume, and cardiac output.
Michard F. Teboul JL. Predicting fluid responsiveness in ICU patients: a critical analysis of the evidence. Chest. 121(6):20008, 2002 Jun.

Scenarios commonly encountered

1- Patients with acute blood losses or body fluid losses 2- Patients with high suspicion of septic shock

3- Patients in the ICU, already resuscitated for several hours or days

After how much & when ? The question is which fluid ?

The Ideal Plasma Volume Expander

Inexpensive No special storage problems; long shelf life Can be made in bulk using existing industrial processes Free of pathogens Nontoxic Crystalloid vs Colloid

Fluid loading: which one ?

Crystalloids greater volume is required incidence of side effect is low Salt loading & hyperchloraemic acidosis Colloids First line product? Risks allergy Hepatotoxic Coagulopathy Nephrotoxic ? Transfusion Not for fluid loading Restrictive strategy ((Hb 7-9 g%)

Task force of the ACCM_SCCM 1999

Time is organ function !!!

Delay in diagnosis Pre-hospital ED Ward ICU Start of treatment

Burden of organ dysfunction

Prognosis

VOLUME EFFECT OF CRYSTALLOIDS

Crystalloid disadvantages
Lowers plasma osmolality Drive water into interstitial space Dilution of plasma protein Decrease in colloidal osm pressure 3 fold amount compared with colloid Hyperchloremic acidosis

Crystalloid disadvantages
Post-op fluid overload increases morbidity significantly Post-op weight gain Post-op confusion Increased duration of post-op ventilation/chest complications

Volume replacement - overview

Crystalloids

Colloids
Natural colloids Artificial colloids

Blood / plasma Crystalloids products

e.g. 0.9 % NaCl Ringers Lactate

Whole blood RBC FFP

Albumin

Gelatin Dextran HES

Plasma proteins

Volume replacement - overview

Sufficient volume effect (efficacy and safety)

stable and reliable constant plateau effect be easily controllable

No plasma accumulation

Requirements of an ideal colloid

Complete renal elimination Excellent safety profile No tissue storage

ALBUMIN
5% Solution - 80% vol expansion 25% Solution 200% vol expansion Effect for 16-24 hrs

Martino P. colloid and crystalloid resuscitation The ICU Book 3rd edit 2007

Advantages
Less anaphylactoid,coaguln abnormalities Volume expansion Antioxidant Inflences acid base status
Barron ME : systemic review of comparative safety of colloids Arch Surg 2004

Disadvantages
Expensive Interstitial Edema - Volume overload

Park G. Molecular mech of drug metabolism in criti ill Brit J. Anesth 1996

Dextran
Dextran 40 and Dextran 70 Volume expansion 100 150% Duration for 6 -12 hrs

Martino P. colloid and crystalloid resuscitation The ICU Book 3rd edit 2007

DEXTRANS
6% dextran 10% dextran 70 40 Mean molecular weight (Dalton). Volume effect (hours) (Approx.). Volume efficacy(%) (Approx.). Maximum daily dose(g/kg). 70,000 5 100

40,000 3-4 175-(200) 1.5

1.5

Adv
Vol expansion higher than HES and 5% albumin Improve Microcirculation. by decreasing viscosity by inhibiting RBCs aggregation
Martino P. colloid and crystalloid resuscitation The ICU Book 3rd edit 2007

Disadv
Anaphylactic reaction Coagulation abnormalities Interfer crossmatch ARF

Barron ME : systemic review of comparative safety of colloids Arch Surg 2004

Gelatins
Succinylated gelatins (gelofusine) Urea crosslinked (haemacel) Oxypolygelatins Volume expansion 70 80 % Duration shorter than alb, HES
Dubois MJ -Periope fluid therapy, 1st edition, 2007

GELATINS
UreaCross linked crossGelatin linked Gelatin. ( Hemaccel ) Concentration (%) 3.5 Mean molecular weight(Dalton) Volume effect(hours) (approx) 35000 1-3 5.5 30000 1-3 Succinylated Gelatin (Gelofusine )

4.0 30000 1-3

Hemacel Na 145 K 5.1 Ca 6.25 Cl 145

Gelofusine Na 154 K 0.4 Ca 0.4 Cl 120

Adv
Cheaper No limit of infusion Less renal effect.

Barron ME : systemic review of comparative safety of colloids Arch Surg 2004

Disadv
Anaphylactoid reaction Effect on coagulation Circulatory dysfunction

Tabuchi N. gelatin impair platelet adhesion in cardiac sx Thromb Haemost 1995

Allergic reactions after application Allergic reactions after application of colloids (%) of colloids (%)
0,4
Allergic reactions (%)

0,2

Gelatins

Dextrans Albumin

HES

prospective multicenter studie (~20.000 patients)

(Laxenaire et al., 1994)

Parameters of HES
Pharmacokinetic and pharmacodynamic of HES is controlled by: Molar substitution C2/C6 Substitution pattern Molecular weight

Volume Effects

The performance of 6% HES as a plasma volume expander is very similar to 5% albumin. The oncotic pressure (30 mm Hg) is higher than 5% albumin (20 mm Hg) the increment in plasma volume can be slightly higher as well

Voluven
The Third Generation HES
Licensed for up to 50ml/kgbw/day Only starch approved for use in pediatrics Only starch approved for use in renal failure patients

VOLUVEN - Less chemical modification

... compared to conventional starches (HES 200/0.5) Voluven has a reduced degree of substitution (by approx. 20 %) improved substitution pattern (C2 /C6 ratio)

Both modifications together ensure a constant renal excretion and avoid plasma accumulation, even after repeated doses

Hot topics with HES

Safety of high dose volume replacement Influence on oxygen tension & inflammatory response Influence on kidney function HES in children

Influence on haemostasis and coagulation

Incidence of anaphylactoid reactions Tissue storage

Original Study with Voluven

Volume effect of 6% HES 130/0.4

(Waitzinger et al., 1998)
Volume effect of 6% HES 130/ 0.4

Study results
Volume effect ~100% Plateau effect ~ 4 hours Volume effect up to 6 hours
hours

LMW HES and tissue oxygenation

Study results Administered : - 6% HES 130/0.4 (Voluven) - Ringer`s Lactate Tissue oxygen tension: - 59% increase with HES 130/0.4 (Voluven) - 23% decrease with RL

SIRS

Can J Anesth 2003; 50 (10): 1009-1016

Intravascular volume replacement with HES 130/0.4 may reduce inflammatory response This is most likely due to an improved microcirculation with reduced endothelial activation and less endothelial damage

High dosage data with Voluven

High dose volume replacement using HES 130/0.4 during major urologic surgery does not alter coagulation (Ellger et al.)

50 ml/kg

Advantages of Voluven at repitive high dose levels in patients with severe craniocerebral trauma (Neff et al.)

70 ml/kg during several days

Safety of High Dose volume substitution with 6%HES 130/0.4 in cardiac surgery (Frey et al.)

48 ml/kg

Large-dose hydroxyethyl starch (HES) 130/0.4 in elective coronary artery bypass surgery (Kasper et al.)

50 ml/Kg

Sticky issues with starch

bleeding tendency caused by inhibition of factor VII and
von Willebrand factor and impaired platelet adhesiveness. This effect is seen predominantly with high MW hetastarch, is less pronounced with medium MW hetastarch, and is absent with low MW hetastarch. The coagulation defect is pronounced when more than 1,500 mL hetastarch is infused within a 24 hr period. can be minimized by limiting the infusion volume to less than 1,500 mL in 24 hours and by avoiding the use of hetastarch in patients with an underlying coagulopathy, particularly von Willebrand's disease.

Acid-base equilibrium before administration of large volumes of an unbalanced solution

Na
+

K+ Ca2+ Mg2+

H
+

PO43 HCO3 Lactat Cl e Alb

SO42, OH etc.

Cation s

Anion s

Acid-base equilibrium after administration of large volumes of an unbalanced solution

Na
+

K+ Ca2+ Mg2+

H
+ PO43 HCO3 Lactat Cl e Alb

Cation s

SO42, OH etc. Anion

Hyperchloremic acidosis
Nausea vomiting Headache Delayed first urination Disturbed blood coagulation Impaired cardiac function Reduced cardiac output Malperfusion of kidneys & gut Inactivation of calcium channels in cell membranes Inhibition of noradrenaline release

Balanced 6% HES 130/0.4

Advantages Due to the same active ingredient as Voluven the same beneficial effects for the patients Balanced electrolyte solution, close to human plasma Lower chloride content than saline based solutions Lowest chloride content as compared to all other balanced solutions With acetate /Malate as a precursor of bicarbonate in order to counteract development of hyperchloraemic metabolic acidosis Carrier solution without Ca2+ ions in order to exclude the risk of complexation of Ca2+ ions with certain anions Disadvantages?

when it comes to selecting the resuscitation fluid doctors are faced with a range of options. At the most basic level the choice is between a colloid or crystalloid solution.

use of 4 percent albumin or normal saline for intravascular volume resuscitation in a heterogeneous population of patients in the ICU Requirements for mechanical ventilation and renal-replacement therapy, time spent in the ICU and in the hospital during the 28day study period, and the time until death (among the patients who died) were also equivalent. The proportion of patients in the two groups in whom new singleorgan or multiple-organ failure developed were similar.

N Engl J Med

2004;350:2247-56

Crystalloid/Colloid Debate
Are colloid more effective than crystalloid? Are synthetic colloid equally effective & safe as human albumin? Do HES have the best risk/benefit profile among all colloids? Is third generations HES safer than olders?

Are colloid more effective than crystalloid?

Hemodynamics changes by colloids are immediate effects and do not lead to improved clinical outcomes in comparison with crystalloids
Finfer S. SAFE Trial, NEJM 2004 Brunkhorst FM. VISEP Trial, NEJM 2008 Wills BA.Comparison of 3 fluids for resuscitation in DSS, NEJM 2005 Upadhyay M. crystalloid and colloid resuscitation in ped septic shock, Indian Pediatri 2005

Are synthetic colloid equally effective & safe as human albumin?

Starches can easily replace albumins as vol expander because they are equally safe but less expensive.
Boldt J. albumin based IV volume replacement in elderly pts undergoing abd sx. Anesth Analg 2007

Recent metaanalysis failed to find mortality benefit of any type colloid in critically ill.
Perel P. colloid vs crystalloids in critically ill, Cochrane data base Review 2009 Bunn F. colloid solutions for resuscitation, Cochrane data base Review 2008

Do HES have the best risk/benefit profile among all colloids?

Dextran associated with anaphylactic reactions,coaguln abnormalities, interfers crossmatch, ARF.
Barron ME : systemic review of comparative safety of colloid , Arch Surg 2004

Gelatins impair platelet function and reduce vWf and coagulation factor VIII:c
Tomi T.,Gelatin and Hydroxyethyl Starch, but Not Albumin, Impair Hemostasis After Cardiac Surgery. Anesth Analg 2006. 2006

Gelatins impair renal function similar to HES 200/0.6 in cardiac surgery.

Boldt J.,Comparison of the effects of gelatin and a modern hydroxyethyl starch solution on renal function and inflammatory response in elderly cardiac surgery patients. Brit J Anesth 2008. 2008

HES 450/0.7 and HES 200/0.5 increases bleeding in cardiac surgery

Haynes GR.,Fluid management in cardiac surgery. J.Cardiothoracic Vasc Anesth 2006.

HES 250/0.45 associated with increased AKI in cardiac surgery.

Rioux JP.,Pentastarch 10% risk factor of AKI following cardiac surgery. Criti Care Med 2009.

Is third generations HES safer than older generations ?

HES 130/0.4 associated with significant reduction in perioperative blood loss
Kozek , effects of HES on blood loss in major sx, analysis of RCT, Anesth Analg 2008

Tetrastarches associated with 15% reduction in blood loss compared to gelatin and pentastarches.
Chang D., colloid for periop plasma expansion: syst review Transf Med 2007

HES 130/0.4 no reported adv effect on renal function.

Boldt J.,influence of vol therapy with modern HES on kidney function Crit Care Med 2007.

HES 130/0.4 not an independent risk factor for adv effect on renal function.
SOAP Trial,.Brit J. Anesth 2007.

9 clinical trials on renal function demonstrate safety of waxy maize derived HES 130/0.4 and, 2 recently published trials confirm that potato derived HES 130/0.42 has no adv effects on renal function.
Westphal M, HES diff products diff effects, Anesthesiology 2009. James MFM, tetrastarches in periop setting, Current opin in Anesthes 2008.

NO MAGIC BULLET Volume therapy should always be customized according to the underlying pathophysiology

Hemodynamic Truths
Tachycardia is never a good thing Hypotension is always pathological CVP is only elevated in disease

THANK YOU