Albumin and Hetastarch for Fluid Resuscitation

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Albumin and Hetastarch for Fluid ResuscitationA Clinical Update

Lisa Courtney, PharmD, Critical Care Resident

Lance Oyen, PharmD, BCPS, Critical Care SpecialistDepartment of Hospital Pharmacy Services

Mayo Clinic, Rochester, MN

FundingSupported by an unrestricted educational grant to the Foundation for Better Health Care (FBHC) from the

members of the Plasma Protein Therapeutics Association (PPTA) and the participating companies includingAlpha Therapeutic Corporation, American Red Cross, Aventis Behring L.L.C., Baxter Healthcare Corporation,

and Bayer Corporation. Sponsored by the Foundation for Better Healthcare.

Faculty Disclosure Information

It is the policy of The Foundation for Better Health Care (FBHC) to ensure balance, independence, objectivityand scientific rigor in all its sponsored educational programs. All faculty are expected to disclose to the

activity audience any real or apparent confict(s) of interest related to the content of their presentation(s).Lisa Courtney, PharmD discloses that she has no relationship or financial interest that impacts this activity.

Lance Oyen, PharmD, BCPS discloses that he has no relationship or financial interest that impacts thisactivity.

Statement of Need

Either crystalloids or colloids may be used for fluid resuscitation of patients with hypovolemic shock,although crystalloids are most commonly used first line. At similar infusion volumes, colloids expand plasma

volume two to four times more than crystalloids, so relatively smaller volumes of colloids are required toexpand the vascular compartment.

Limitations with colloid therapy include coagulopathy, transfusion reactions, and costs. Hence, colloids havesome benefits and limitations relative to crystalloid therapy. The two most commonly used colloids forintravascular volume expansion are albumin and hydroxyethyl starch (HES), which have similar colloid

oncotic properties. Although HES is typically less expensive than albumin, several studies have shown that ican have adverse effects on coagulation that may be costly to treat. Albumin has several theoretical

biological benefits, including antioxidant activity and binding of membrane lipids. A meta-analysis ofrandomized controlled trials linked albumin with increased mortality; some limitations of this metaanalysis

include patient selection and disease heterogeneity. With that said, colloids still have therapeutic utility in

the management of shock states.

CPE Credit Designation

The FBHC is approved by the American Council on Pharmaceutical Education as a provider of continuingpharmaceutical education. This program has been assigned the Universal Program Number 098-000-03-999

H01 and has been approved for 2 contact hours (0.2 CEUs). Credit for the posttest is available until June 1,2005. A minimum of 70 percent correct must be obtained in order for credit to be awarded by the FBHC.

There is no fee for this activity.

Intended AudienceThis activity is intended for hospital pharmacists.

Goal


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The goal of this activity is to update pharmacists on the similarities and differences between albumin andhetastarch for fluid therapy, including guidelines for use, clinical considerations, adverse effects, and new

pharmacoeconomic issues.

Learning ObjectivesAfter reading this article, the pharmacist should be able to:

State the physiologic and pharmacologic effects of albumin and hetastarch.

Delineate the indications for fluid therapy and guidelines for use of albumin and hetastarch.

Explain how these agents affect the coagulation system.

Discuss how the choice of a fluid resuscitation agent can affect outcomes, including adverse events

and cost.

METHOD OF PARTICIPATIONThis activity should take approximately 2 hours to complete. The participant should, in order, read thearticle, complete the post-test, complete the registration and evaluation forms. To access the post-test form

registration and evaluation click on the "CPE Post-Test" icon at the end of the article. To receive credit forthis activity, follow the instructions provided on the post-test. This credit is valid through June 1, 2005. No

credit will be given on the posttest after this date. Users who receive a successful online grade of 70%, or

better, will be issued a CPE certificate for 2.0 CPE credit online that may be printed at their location. In theevent that you are unable to print a certificate, please email the [email protected] indicating that you could

not print a certificate and a certificate will be mailed to you within two weeks.

Unlabeled/Unapproved Uses of Drugs or Devices

Some discussion in this document may reflect unapproved uses for some products. Readers areencouraged to consult appropriate resources, including full prescribing information for any

product or device mentioned in this activity.

DisclaimerThe views expressed are those of the FBHC. It should not be inferred or assumed that this activity expresse

the views of any manufacturer of pharmaceuticals. The FBHC is an independent professional organization

that does not endorse specific products of any pharmaceutical concern.

The recommendations discussed in the following pages are intended as examples consistent with sound

medical practice. Other techniques and practices exist.

All rights reserved, including translation into other languages. No part of this publication may be reproducedor transmitted in any form or by any means-electronic or mechanical, including photocopying, recording, or

storage in information storage and retrieval systems-without permission in writing from The Foundation forBetter Health Care, 6 East 32 Street, New York, NY 10016.

Copyright 2003, The FBHC.

Albumin and Hetastarch for Fluid Resuscitation

A Clinical Update

Traditionally, body fluid has been divided into two compartments, or spaces, intracellular and extracellular.

The extracellular compartment has been subdivided into intravascular and interstitial compartments. Truehypovolemia, or volume depletion, may be defined as a reduction in both intracellular and extracellular fluid

with loss outside the body, and it may occur in a wide range of disorders and conditions. Acute hypovolemiarequiring fluid resuscitation can develop when fluid losses occur rapidly resulting in shock or impending

shock, as in hemorrhage, burns, surgery, or other trauma in which vascular volume deficit is present. Other
mailto:[email protected]:[email protected]


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nontraumatic causes of acute hypovolemia requiring fluid resuscitation could include rapid loss ofgastrointestinal fluid through severe vomiting, diarrhea, tube drainage without adequate replacement,

marked dehydration secondary to skin losses from excessive sweating or certain dermatoses (eg,pemphigus), and renal losses secondary to profound diuresis. Occasionally, redistribution of fluid from the

vascular to the interstitial compartment without actual loss to the external environment may provoke acutehypovolemia requiring fluid resuscitation. This may occur in acute pancreatitis, bowel infarction, or septic

shock. Redistribution hypovolemia usually is a result of vasodilation and a capillary leak phenomenon causeby diffuse inflammation and its mediators.

The clinical features of acute hypovolemia, regardless of the cause, depend on the rate and magnitude ofvolume loss along with the response of the cardiovascular system to volume reduction . The major

hemodynamic abnormality is decreased venous return to the heart. Cardiac output and blood pressure are

maintained initially by sympathetically mediated increases in heart rate, myocardial contractility, and arteriavasoconstriction. This may be manifested clinically by tachycardia and a decreased pulse pressure (the

difference between systolic and diastolic pressure). These pathophysiologic responses can compensate for aintravascular volume loss of up to 30% to 40%. When the magnitude of volume loss exceeds this amount,

compensatory mechanisms are inadequate, and hypovolemic shock with perfusion deficits results . 1 , 2

Hypovolemic ShockThe signs of hypovolemic shock are falling systolic blood pressure (


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Currently, the three broad categories of intravascular fluid therapies are oxygen-carrying fluids (typically

whole blood or packed red cells), crystalloid solutions, and colloidal solutions. With the possible exception ofsevere hemorrhagic shock, there are few circumstances in which whole blood is administered for fluid

resuscitation.6 Crystalloids and/or colloids are used for fluid resuscitation when whole blood is unavailableand in other clinical settings, including the management of mild to moderate hemorrhagic shock (15% to

20% blood loss)1,7 and the initial treatment of massive hemorrhagic shock.

Crystalloids: Crystalloid solutions contain electrolytes dissolved in water, with or without dextrose. The

crystalloids most commonly used clinically are 0.9% sodium chloride and lactated Ringer's solution (whichcontains sodium chloride, calcium chloride, potassium chloride, and sodium lactate). Both are isotonic with

plasma, freely cross intact capillary membranes to distribute within the extracellular compartment, and hav

no particles with a molecular weight (MW) greater than 10,000 d.8 For every liter of crystalloid fluid infused750 mL enter the interstitial compartment

and only 250 mL remain in the vascular compartment. 6 Consequently, relatively large volumes are required

to expand the intravascular space during fluid resuscitation. Crystalloids are inexpensive, readily available,and easily stored. They cause few adverse reactions and can quickly correct most acute volume deficits.

Crystalloids are the most commonly used fluids for resuscitation. The American College of SurgeonsCommittee on Trauma and the Institutes of Health recommend lactated Ringer's solution as the crystalloid o

choice in initial fluid resuscitation.3,9,10

Because a large proportion of the crystalloid administered is sequestered in the interstitial compartment,peripheral edema often occurs in patients receiving more than 10 L of these solutions in 24 hours.8 A major

point in the crystalloidcolloid debate is the consequent risk of pulmonary edema associated with large-volume crystalloid resuscitation.5,11,12,13 In addition, the Institutes of Health document potential adverse

immunologic consequences, including increased expression of adhesion molecules, release ofproinflammatory cytokines, and apoptosis associated with fluid resuscitation with lactated Ringer's

solution.5,11

Colloids: Colloidal solutions contain large, oncotically active molecules derived from natural products (eg,albumin, gelatin) or from synthetic, nonprotein products (eg, carbohydrates such as starches or dextrans)

that are distributed throughout a dispersion medium such as water. Compared with crystalloids, colloids aremore impermeable to intact capillary membranes. The oncotic pressure they exert preferentially expands thvascular compartment with little loss into the interstitial compartment. Accordingly, comparatively smaller

volumes of colloids than crystalloids are required for fluid resuscitation. At similar infusion volumes, colloids

expand the plasma volume two to four times more than crystalloids.6 Since the relatively large molecules incolloidal solutions persist intravascularly, colloids have a longer duration of action than crystalloids. Colloida

solutions available for clinical use include 5%, 20%, and 25% human serum albumin; 6% hydroxyethyl starh (HES; hetastarch); 5% human plasma protein fraction (PPF); a mixture of proteins prepared from pooled

blood; fresh frozen plasma; oxypolygelatin (a polymer of urea and polypeptides derived from denature d


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gelatin); gelatin polysuccinate; and dextran (a polymer of D-glucose, with specific pre parations designatedaccording to their average MW, such as dextran 40 [MW = 40,000 d] and dextran 70 [MW = 70,000 d]).

Albumin and HES are the two colloids administered most frequently for intravascular volume expansion inthe U.S.14 The relative utility of these fluids for the management of acute hypovolemia has been the subject

of ongoing controversy and is addressed in the remainder of this supplement.

Limitations with colloid therapy include pulmonary edema, coagulopathy, transfusion reactions, and costs.Pulmonary edema can occur with fluid resuscitation using colloids and crystalloids. Chills, urticaria, fever,

and vasodilation can occur with albumin, as with transfusion reactions. Coagulopathy has been associated

with hetastarch. With the rise in healthcare costs, albumin and hetastarch are more expensive agents thancrystalloids.

AlbuminAlbumin, the predominant protein in human plasma, consists of 575 amino acids,5,15 with a MW of about

69,000 d.5,16 It carries a negative charge of 17 at physiologic pH.5,15 Although albumin represents only about60% of plasma protein by weight, it accounts for about 75% to 80% of the normal colloid oncotic pressure .1,5 This oncotic pressure is determined by the number of molecules in a fluid rather than by their weight(Table 1) .16

As a result of albumin's oncotic activity, 1 g of albumin draws about 18 mL of water, depending on plasma

pH and protein concentration, from the interstitial compartment to the vascular compartment. 8,15 Forexample, when 25 g of albumin are infused, the intravascular volume expands by about 450 mL over the

next 30 to 60 minutes. The plasma half-life of administered albumin usually ranges from 12 to 16 hours butmay be shorter in patients with shock or sepsis.8

Theoretical Utility of Albumin: In addition to its role in regulating plasma volume and fluid balance, albumin

binds circulating bilirubin, a number of circulating lipids, metabolites, hormones, enzymes, and drugs. 17Albumin provides a number of other potentially beneficial biologic effects such as antioxidant activity and

binding with membrane lipids, which could confer a protective effect in clinical settings where an increase incolloid oncotic pressure in conjunction with fluid resuscitation might be required. 18,19

A major concern with fluid resuscitation is the production of oxygen-derived free radicals during reperfusion

of previously ischemic tissues. This can activate the inflammatory cascade and produce significant cellularinjury.11 Published reports suggest that albumin acts as a scavenger of free radicals to limit lipid

peroxidation. Quinlan et al observed that administration of albumin to patients with sepsis syndrome, whoare known to suffer from oxidative stress, led to a sustained increase in plasma thiols, which have several

important antioxidant functions.18 Soejima et al showed that serum albumin may inhibit peroxidation of

erythrocyte membrane lipids, which could contribute to oxidative cell damage in patients undergoing chronichemodialysis.19 Most recently, Rhee et al determined that neutrophil activation and expression of neutrophil

adhesion molecules, a potential pathogenetic mediator of cellular injury, were significantly increased by

crystalloids and certain colloids (ie, HES and dextran) but not by albumin.20

Commercial Preparations: Albumin is prepared commercially from pooled donor plasma. To eliminate the

risk of transmitting viral infections, donor plasma is first screened for hepatitis B, hepatitis C, humanimmunodeficiency virus, syphilis, and enzyme markers of liver disease. Cryoprecipitate, factor VIIIconcentrate, and factor IX complex are separated from the pooled plasma, and the remainder is fractionate

into albumin, immune globulin, and other factors. The pooled albumin fraction is then heated for 10 hours a60oC (pasteurized).

Albumin (human) USP is commercially available as 5%, 20%, and 25% solutions (ie, 5 g, 20 g, and 25 g of

albumin per 100 mL, respectively) under several brand names. The 5% solutions are isotonic and isoosmotiwith plasma, while the 20% and 25% solutions are isotonic but hyperosmotic compared with plasma. At the


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recommended temperature of no higher than 30C, albumin can be stored for 3 years.

Albumin is administered by intravenous infusion. Labeled dosing recommendations differ according to theconcentration of albumin solution and the specific indication for use. Labeled dosing recommendations also

differ by brand for otherwise equivalent concentrations and volumes of albumin. The reader is there foreurged to consult the specific product labeling for dosage inform ation. Albumin is relatively safe, with its rar

adverse effects limited to hypersensitivity reactions or to protein overload due to high dosage or repeatedadministration in patients with low cardiac reserve.

Limitations of Albumin: With albumin, the risk of an anaphylactoid reaction is 0.011% (1/8 the riskassociated with hetastarch).14 Other transfusion reactions include chills, urticaria, fever, and vasodilation.5

Albumin may be administered without provoking an immunologic reaction, regardless of a patient's blood

group or Rh factor. A complication that may occur in patients receiving 25% albumin therapy is a reductionin glomerular filtration rate.5

Although albumin products of equivalent concentration are presumed to be therapeutically equivalent,

labeled indications differ by brand and occasionally are contradictory. The reader is therefore urged toconsult the individual product labeling for specific indications. Table 2 summarizes the labeled indications

for albumin 5%, 20%, and 25% and for 6% hetastarch, and product availability.

Guidelines for Use: There remains an ongoing crystalloid-colloid debate regarding the optimal therapy forfluid resuscitation, and consensus guidelines as well as institutional guidelines for


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the clinical use of resuscitation fluids have been developed. The University Hospital Consortium (UHC), analliance of 65 U.S. academic medical centers, completed comprehensive model guidelines for the appropriat

and efficient use of albumin, nonprotein colloid, and crystalloid solutions in 1993 (published in 1995). 21 Todevelop the guidelines, a group of 24 participants from 26 of the member institutions reviewed the literatur

from 1977 through 1993. Their responses to questions regarding the clinical utility of these solutions werestatistically analyzed in a systematic consensus-development process (the Delphi method). Five separate

questionnaire rounds were designed to establish fluid replacement criteria for 12 clinical indications. Theoverall conclusion was that crystalloids should be considered the fluid of choice or the recommended fluid fo

essentially all clinical indications offering a choice (ie, hemorrhagic shock, nonhemorrhagic shock, hepaticresection, thermal injury, cerebral ischemia, cardiac surgery, and cirrhosis and paracentesis). The

consortium determined, however, that use of albumin may be warranted under certain specific

circumstances in some clinical settings (ie, hemorrhagic shock, nonhemorrhagic shock, hepatic resection,thermal injury, nutritional intervention, cardiac surgery, hyperbilirubinemia of the newborn, cirrhosis and


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paracentesis, nephrotic syndrome, organ transplantation, and plasmapheresis). Of note, revised UHCguidelines are expected to be released in 2000 that should include the impact of the albumin meta-analysis

on therapeutic guidelines.

The UHC guidelines originally published in 1995 were reprinted in their entirety in U.S. Pharmacist inDecember 199822 and will not be reproduced here. With respect to hemorrhagic shock, the 1995 guidelines

state that crystalloids should be considered the initial resuscitation fluid of choice. Colloids are appropriatefor fluid resuscitation in conjunction with crystalloids when blood products are not immediately available. On

the basis of cost-effectiveness considerations, nonprotein colloids are favored over albumin, except in the

following cases: 1) if nonprotein colloids are contraindicated, use of 5% albumin is recommended, and 2) ifsodium restriction is required, the use of 25% albumin, diluted to 5% with 5% dextrose solution, is

recommended. Normal saline is an appropriate diluent unless sodium restriction is required, but sterile wate

should never be used to dilute 25% albumin, because the resulting hypoosmolar solution can cause severehemolysis.23 Relative contraindications to the use of nonprotein colloids include, but may not be limited to,

the following: 1) previous hypersensitivity to the components of the solution, 2) underlying bleedingdisorders, 3) risk of intracranial hemorrhage, and 4) renal failure with either oliguria or anuria. Crystalloid

and colloid solutions should not be considered substitutes for blood or blood components when oxygen-carrying capacity is reduced and/or when replenishment of clotting factors or platelets is required.

Other guidelines on the use of albumin are widely available. For example, Drug Facts and Comparisons lists

shock and burns as appropriate indications for 5% albumin solutions, but use of albumin as a nutrient inpatients with hypoproteinemia is not recommended.24 Hypoproteinemia with or without edema, burns,

shock, erythrocyte resuspension, acute nephrosis, renal dialysis, and hyperbilirubinemia and erythroblastosifetalis are listed as appropriate indications for 25% albumin solutions.

Institutional guidelines for albumin have also been promulgated. The 1997 Los Angeles County/USC Medical

Center trauma surgery and critical care guidelines for albumin and hetastarch list six indications.25 Accordinto these guidelines, before albumin is administered, a clinical goal should be determined and the patient's

baseline serum albumin level should be measured; if the baseline level is higher than 2.2 g/dL, albuminshould not be given.

Patients who require an oncotic load and volume replacement should receive 5% albumin, and those whose

fluid and sodium intake must be minimized should receive 25% albumin. Albumin should not be ordered ona continuous basis such as "Albumin 5% 500 mL q 6 hr."

Meta-analysis of Clinical Studies: It has been proposed that administration of albumin in the presence of a

persistent capillary leak may promote the movement of fluid from the vascular to the interstitial

compartment, aggravating hemorrhage-induced hypotension.11 To help resolve this and other issuessurrounding the use of crystalloid and colloid solutions for fluid resuscitation, Schierhout and Roberts26 and

the Cochrane Injuries Group Albumin Reviewers27 in 1998 published meta-analyses of randomized controlled

trials comparing albumin or PPF with no fluid therapy or crystalloid administration in critically ill patients withypovolemia. Schierhout and Roberts26 concluded that, compared with fluid resuscitation with crystalloids,

fluid resuscitation with colloidal solutions was associated with an absolute increase in the risk of mortality.

The Cochrane group27

concluded that administration of albumin does not reduce mortality among critically ilpatients with hypovolemia, burns, or hypoalbuminemia and, compared with administration of crystalloids,actually may increase mortality.

The meta-analysis has been criticized for its reliance on studies that used small numbers of patients and

patients with different diseases, and for its use of death as the single end point.11,28 It prompted responsesfrom several clinicians who disagreed with its findings.29-34 For example, Bapat and Raine29 noted that,

although dextran 70 was clearly associated with greater mortality than crystalloids, the difference betweenother colloids and crystalloids was not significant. They observed, "the only interpretation one can draw from


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this review is that use of dextran 70 for fluid resuscitation in critically ill patients is associated with a highermortality than use of other colloids." Wyncoll and colleagues30 noted that the conclusion drawn by Schierhou

and Roberts was flawed and not supported by the meta-analysis, since the study groups were far tooheterogeneous to allow a meaningful comparison. Bell31 questioned the reliability of the evidence supporting

the effects of albumin administration in critically ill patients, which raised questions about the best methodsfor communicating future findings to the profession.

Watts32 noted that another recent review, by Hankeln and Beez,33 found a conclusion opposite that of the

metaanalysis, specifically that colloids are more effective than crystalloids in optimizing physiologic variable

related to blood flow in critically ill patients. These reviewers found that crystalloids are less effective thancolloids in improving cardiac output and oxygen delivery and in preventing tissue perfusion defects.

McAnulty and Grounds noted that only five of the studies included in the meta-analysis compared commonly

used resuscitation fluids, and in four of these studies mortality was lower with colloids than withcrystalloids.34

Hydroxyethyl Starch

Hetastarch is a synthetic colloid derived from a waxy starch composed almost entirely of amylopectin, abranched-chain polyglucose that resembles glycogen. Hydroxyethyl groups are introduced into the glucose

units of the starch, and the resultant material is hydrolyzed to yield a product whose MW makes it suitablefor use as a plasma volume expander. The MW ranges from 1000 d to greater than 3,000,000 d, with an

average MW of 45,000.5 Molecules smaller than 50,000 d are rapidly eliminated renally, with a plasma half-life of approximately 24 to 36 hours.5 Hetastarch is available commercially as a 6% solution (ie, 6 g of HES

per 100 mL) in 500-mL containers. The colloidal oncotic properties of HES approximate those of albumin,and it expands intravascular volume equally effectively.14 Although albumin and HES possess similar volume

expanding properties, these colloids differ substantially in many ways, and, unlike HES, albumin is a keyparticipant in a number of other important physiologic activities.

Commercial Preparations, Indications, and Guidelines for Use: Commercially available preparations of 6%

HES and their indications are listed in Table 2. The labeled indication for HES is treatment of hypovolemia.The indications for HES listed in Drug Facts and Comparisons are as an adjunct for plasma volume expansio

in shock due to hemorrhage, burns, sepsis, surgery, or other trauma, and for leukapheresis.35 For volumeexpansion, the total dosage does not usually exceed 1500 mL/day (20 mL/kg).35 The 1995 UHC guidelines

noted that, "on the basis of cost-effectiveness considerations, nonprotein colloids are favored over albumin"for hemorrhagic shock unless nonprotein colloids are contraindicated.27 Relative contraindications to the use

of HES and other nonprotein colloids include, but may not be limited to, previous hypersensitivity to thesolution components, underlying bleeding disorder, risk of serious intracranial hemorrhage, and renal failure

with either oliguria or anuria. The risk of an anaphylactoid reaction is 0.085% (1 in 1200).14 A potential

adverse effect of HES is its effect on coagulopathies.

Effect on Coagulation: In 1997, Warren and Durieux reviewed 18 published reports of the effect of HES on

the coagulation process.14 Of those reviewed, six showed no effect of HES on coagulation, eight showedadverse effects on laboratory values only, and four showed clinically significant bleeding. Most of the studie

revealed decreases in factor VIII, fibrinogen, and von Willebrand factor, with increases in partial

thromboplastin time, prothrombin time, and bleeding time after doses of 500 mL to 1000 mL of HES. Themechanism of action remains unknown, but the authors hypothesized that HES may precipitate certaincoagulation factors or form complexes and accelerate the action of thrombin and the conversion of

fibrinogen to fibrin. This last effect not only reduces the amount of fibrinogen available for normalcoagulation but also produces a fibrin clot that is lysed more easily. Hetastarch may also impair platelet

function. The authors concluded that "HES should be used with caution, especially where bleeding wouldpotentially be of serious consequence to the patient."14

A number of recently published studies support this conclusion. Egli and co-workers compared the effect of


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progressive hemodilution with HES, gelatin, or albumin on blood coagulation.36 Hemodilution with each ofthe three colloids significantly compromised coagulation time and thromboelastographic variables (p800 mL over 4

hours, or surgeon-diagnosed excessive intraoperative bleeding), the investigators identified 93 of 511cardiothoracic surgery patients (18%) who met that definition. In the first study, it was shown that

unadjusted hospital costs were $3458 higher for patients who experienced hemorrhage than for controls.After this study was completed, HES was substituted for albumin as the pump-priming solution to reduce

cost, with an anticipated savings as great as $53,000 annually. Because hemorrhage rates increased afterHES was substituted for albumin, a second case-control study was performed, which identified patient age

(p=0.02) and use of >5 mL/kg HES (p=0.05) as significant risk factors for hemorrhage (Table 3). The costof treating these episodes of hemorrhage exceeded all estimates of possible product cost savings associated

with HES. The investigators concluded that "efforts to save money by substituting less expensive productsmay inadvertently increase costs by increasing the probability of perioperative adverse events." The results

of this study prompted discontinuation of the use of HES and resumption of the use of albumin as the

priming fluid.


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ConclusionsCrystalloids are the resuscitation fluid of first choice in essentially all clinical settings other than massive

hemorrhagic shock. Colloids are appropriate for fluid resuscitation in conjunction with crystalloids in certainclinical situations, including but not limited to the need for sodium restriction, failure of crystalloids to

correct hypovolemia in burn patients, and during cardiac surgery when it is crucial to avoid pulmonaryinterstitial fluid accumulation. Albumin and HES are the two colloids administered most frequently for fluidresuscitation. These colloids offer theoretical advantages over crystalloid solutions for treatment of

hypovolemic shock, particularly their prolonged intravascular retention time compared with crystalloids.

Albumin binds circulating bilirubin and certain lipids, metabolites, hormones, enzymes, and drugs, and itprovides a number of other potentially beneficial biologic effects. However, albumin is typically more

expensive than HES. A controversial meta-analysis of randomized controlled trials linked albumin withincreased mortality. A number of studies have shown that HES can adversely affect coagulation, and the

treatment of resultant bleeding may increase cost. The choice between albumin and HES should be madebased on the characteristics of each and the specific clinical setting in which colloid will be used.

REFERENCES

1. Arrigoni LE, Rogers DK. Intensive care therapeutics. In: Young LY, Koda-Kimble MA, eds. Applied

Therapeutics: The Clinical Use of Drugs, 6th ed. Vancouver, Wash: Applied Therapeutics, Inc.;1995:18.1-18.35.

2. Guyton AC. Textbook of Medical Physiology, 9th ed. Philadelphia, Pa: W.B. Saunders

Company;1996:285-294.

3. Pathophysiology of acute hemorrhagic shock. In: Pope A, French G, Longnecker DE, eds. Fluid

Resuscitation: State of the Science for Treating Combat Casualties and Civilian Injuries. Washington,

DC: National Academy Press; 1999:19-46.

4. McConkey DJ, Bold RJ. Cellular Signaling and Cell Death. In: Shoemaker WC, Ayers SM, Grenvik A,

Holbrook PR, eds. Textbook of Critical Care, 4th ed. Philadelphia, Pa: W.B. Saunders Company, 2000

586-596.

5. Roberts JS, Bratton SL. Colloid volume expanders: problems, pitfalls and possibilities. Drugs. 1998.

May:55(5)621-630.

6. Kokko JP. Disorders of fluid volume, electrolyte, and acid-base volume. In: Bennett JC, Plum F, eds.

Cecil Textbook of Medicine, 20th ed. Philadelphia, Pa: W.B. Saunders Company; 1996:525-532.

7. Shoemaker WC. Resuscitation algorithms in acute emergency conditions. In: Shoemaker WC, Ayers

SM, Grenvik A, Holbrook PR, eds. Textbook of Critical Care, 4th ed. Philadelphia, Pa: W.B. Saunders

Company, 2000: 47-59.

8. Wilson RF. Critical Care Manual:Applied Physiology and Principles of Therapy, 2nd ed. Philadelphia,

Pa: F.A. Davis Company; 1992:223- 286.


12/13

9. American College of Surgeons. Shock. In: Alexander RH, Proctor HJ, eds.Advanced Trauma Life

Support Instructor Manual, 5th ed. Chicago, Ill, American College of Surgeons, 1993:76-94.

10. Asensio JA, Hanpeter D, Gomez H, Chahwan S, Orduna S, McDuffie L. Exsanguination. In: Shoemake

WC, Ayers SM, Grenvik A, Holbrook PR, eds. Textbook of Critical Care, 4th ed. Philadelphia, Pa: W.B

Saunders Company, 2000:37-47.

11. Experience with and complications of fluid resuscitation. In: Pope A, French G, Longnecker DE, eds.Fluid Resuscitation: State of the Science for Treating Combat Casualties and Civilian Injuries.

Washington, DC: National Academy Press; 1999:47-76.

12. Shoemaker WC. Pathophysiology and management of acute respiratory distress syndrome after

surgery, trauma, and other acute illnesses. In: Shoemaker WC, Ayers SM, Grenvik A, Holbrook PR,

eds. Textbook of Critical Care, 4th ed. Philadelphia, Pa: W.B. Saunders Company, 2000:1393-1404.

13. Erstad BL. Hypovolemic Shock. In: Dipiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM,

eds. Pharmacotherapy: a pathophysiologic approach, 4th ed. Stamford, CT: Appleton and Lange,

1999:408-421.

14. Warren BB, Durieux ME. Hydroxyethyl starch: safe or not?Anesth Analg 1997;34:206-212.

15. Layon AJ, Kirby RR. Fluids and electrolytes in the critically ill. In: Civetta JM, Taylor RW, Kirby RR,

eds. Critical Care. Philadelphia, Pa: J.B. Lippincott Company; 1988:451-474.

16. Guyton AC. Textbook of Medical Physiology, 9th ed. Philadelphia, Pa: W.B. Saunders Company;1996:183-197.

17. Emerson TF Jr. Unique features of albumin: a brief review. Crit Care Med1989;17:690-694.

18. Quinlan GJ, Margason MP, Mumby S, Evans TW, Gutteridge JM. Administration of albumin to patients

with sepsis syndrome: a possible beneficial role in plasma thiol repletion. Clin Sci1998;95:459-465.

19. Soejima A, Matsuzawa N, Miyake N, et al. Hypoalbuminemia accelerates erythrocyte membrane lipid

peroxidation in chronic hemodialysis patients. Clin Nephrol1999;51:92-97.

20. Rhee P, Wang D, Ruff P, et al. Human neutrophil activation and increased adhesion by various

resuscitation fluids. Crit Care Med2000;28:74-78.

21. Vermeulin LC Jr, Ratko TA, Erstad BL, et al. A paradigm for consensus: the University Hospital

Consortium guidelines for the use of albumin, nonprotein colloid, and crystalloid solutions.ArchIntern Med1995;155:373-379.

22. Gonzalez ER, Kannewurf BS. Clinical review of appropriate uses for albumin. US PharmacistDecember 1998:1-12.

23. Steinmuller DR. A dangerous er ror in the dilution of 25 percent albumin. N Engl J Med

1998;338:1227.

24. Albumin human (normal serum albumin). In: Drug Facts and Comparisons. St. Louis, Missouri: Facts

and Comparisons; 2000:207-208.25. Los Angeles County, University of Southern California Trauma Surgery and Critical Care.

Albumin/hetastarch guidelines: protocol. March 20, 1997.www.usc.edu/hsc/medicine/surgery/trauma/ trauma_protocols/icu-06-albumin.html.

26. Schierhout G, Roberts I. Fluid resuscitation with colloid or crystalloid solutions in critically ill patients

a systematic review of randomised trials. Br Med J1998;316:961-964.

27. Cochrane Injuries Group Albumin Reviewers. Human albumin administration in critically ill patients:

systematic review of randomized controlled trials. Br Med J1998;317:235-240.28. Erstad BL. Concerns with defining appropriate uses of albumin by meta-analysis.Am J Health Syst

Pharm. 1999;56:1451-1454.

29. Bapat PP, Raine GJ. Fluid resuscitation with colloid or crystalloid solutions. Use of dextran-70 for fluid

resuscitation has been dying out. Br Med J1998;317:277. Letter.

30. Wyncoll DLA, Beale RJ, McLuckie A. Fluid resuscitation with colloid or crystalloid solutions. Conditions

and patient groups were too heterogeneous to allow meaningful comparisons. Br Med J1998;317:278- 279. Letter.


13/13

31. Bell E. The dud cigar?Cochrane collaboration and the saga of human albumin. Adverse Drug React

Toxicol Rev1999;18:149-163.

32. Watts J. Comparing different studies is difficult. Br Med J1998;317:277.

33. Hankeln K, Beez M. Haemodynamic and oxygen transport correlates of various volume substitutes in

critically ill in-patients with various aetiologies of haemo-dynamic instability. Int J Intensive Care

1998;5:8-14.34. McAnulty GR, Grounds RM. Eight studies should have been excluded. Br Med J1998;317:277.

35. Hetastarch (Hydroxyethyl starch; HES). Drug Facts and Comparisons. St. Louis, Mo: Facts and

Comparisons; 2000:209.

36. Egli GA, Zollinger A, Seifert B, et al. Effect of progressive haemodilution with hydroxyethyl starch,

gelatin and albumin on blood coagulation. Br J Anaesthesiol1997;78:684-689.

37. Niemi TT, Kuitunen AH. Hydroxyethyl starch impairs in vitro coagulation.Acta Anaesthesiol Scand

1998; 42:1104-1109.

38. Cope JT, Banks D, Mauney MC, et al. Intraoperative hetastarch infusion impairs hemostasis after

cardiac operations.Ann Thorac Surg 1997;63:78-83.

39. Omar MN, Shouk TA, Khaleq MA. Activity of blood coagulation and fibrinolysis during and after

hydroxyethyl starch (HES) colloidal volume replacement. Clin Biochem 1999;32:269-274.

40. Knutson JE, Deering JA, Hall FW, et al. Does intraoperative hetastarch administration increase bloodloss and transfusion requirements after cardiac surgery?Anesth Analg 2000;90:801-807.

41. Herwaldt LA, Swartzendruber SK, Edmond MB, et al. The epidemiology of hemorrhage related to

cardiothoracic operations. Infect Control Hosp Epidemiol1998;19:9-16.

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