fluid choice for resuscitation of the trauma

7/28/2019 Fluid Choice for Resuscitation of the Trauma

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1 NEUROANESTHESIA AND INTENSIVE CARE

Fluid choice for resuscitation of the traumapatient: a review of the physiological, pharmaco-

logical, and clinical evidence[Le choix du liquide pour la ranimation du patient polytraumatis: une revue

des donnes physiologiques, pharmacologiques et cliniques]

Joachim Boldt MD PhD


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2 NEUR OANE STHE SIA AND INTENSIVE C ARE

Purpose : Volume replacement regimens are discussed very

emotionally. Interpretation of the literature is difficult due to variations

in study design, patient population, target for volume replacement,

endpoints, and type of fluids. Meta-analyses may not be very helpful

because all kinds of patients and very old studies are included. The

principles and options for volume replacement were reviewed

exclusively in trauma patients and studies from the literature focusing

on this problem were analyzed.

Source: Using a MEDLINE search, volume replacement therapy in

adult trauma patients published in the English language from 1985 to

the end of 2002 were identified and analyzed. Studies on prehospital

volume replacement, volume replacement in the emergency area or in

the operating room, and volume therapy in trauma intensive care unit

patients were included.

Principle findings: The age-old crystalloid/colloid controvery

has still not been resolved but has been enlarged to a colloid/colloid

debate. It is now widely accepted that human albumin could easily be

replaced by synthetic colloids for volume replacement in traumapatients. No superiority of a specific volume replacement strategy with

regard to outcome was found. However, in several studies outcome

was not the major endpoint. Although showing some promising results,

the importance of hypertonic solutions for volume replacement in the

trauma patient is not yet defined.

Conclusion: The choice of fluid therapy in trauma patients engen-

ders the most controversy and an examination of the body of literature

on this subject results in confusion. It is imperative to continue the

search for substances that are effective in avoiding the development of

post-trauma multi-organ dysfunction syndrome without detrimental

side-effects.

Objectif: Les doses de rem plissage vasculaire suscitent des discus-

sions trs motives. Linterprtation des publications est difficile

cause de la diversit des devis dtudes, des populations de patients,

des cibles de remplissage vasculaire, des paramtres tudis et des

types de liquides. Les mta-analyses ne sont peut-tre pas trs utiles

parce quelles comprennent tous les types de patients et danciennes

tudes. Les principes qui rgissent le remplissage vasculaire et les

options offertes ont t revus exclusivement chez les polytraumatiss

et les tudes qui mettent laccent sur ce problme ont t analyses.

Source : Les articles sur le remplissage vasculaire ralis chez les

patients polytraumatiss et rapports en anglais entre 1985 et la fin de

2002 ont t reprs dans MEDLINE et analyss. Les tudes sur le

remplissage vasculaire prhospitalier, sur le remplissage vasculaire

lurgence ou en salle dopration et sur le remplissage vasculaire chez

les patients polytraumatiss de lunit des soins intensifs ont t

retenues.

Constatations principales : La sempiternelle controverse cristal-

lode/collode nest pas encore rsolue, et sest tendue au dbat col-

lode/collode. On accepte gnralement de remplacer lalbumine

humaine par des collodes synthtiques chez les polytraumatiss. Nous

navons trouv aucune stratgie de remplissage vasculaire qui soit

suprieure aux autres quant au rsultat. De toute manire, le rsultat

ntait pas toujours le paramtre principal. Mme si les solutions

hypertoniques ont prsent quelques rsultats prometteurs, leur

importance dans le rem plissage vasculaire chez les polytraumatiss

nest pas encore dfinie.

Conclusion : Le choix dune fluidothrapie chez les polytraumatiss

engendre la plus grande controverse. Lexamen des publications sur le

sujet napporte que confusion. Il faut poursuivre la recherche de sub-

stances efficaces, qui noccasionnent pas de dficiences polyviscrales

post-traumatiques et qui soient sans effets secondaires nocifs.


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3 NEUR OANE STHE SIA AND INTENSIVE C ARE

From the Department of Anesthesiology and Intensive Care Medicine, Klinikum der Stadt Ludwigshafen, Ludwigshafen,

Germany.

Address correspondence to: Prof. Dr. Joachim Boldt, Department of Anesthesiology and Intensive Care Medicine, Klinikum

der Stadt Ludwigshafen, Bremserstr. 79, D-67063 Ludwigshafen, Germany. Fax: 0621-503-3024;E-mail: [email protected]

Manuscript assessed May 20, 2003.Accepted for publication September 16, 2003.

Revision accepted February 13, 2004.

CAN J ANESTH 2004 / 51: 5 / pp 500513
mailto:[email protected]:[email protected]:[email protected]


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Boldt: VOLUME REPLACEMENT IN TRAUMA PATIENTS 4

RAUMA is the fourth-leading cause of death in the USA.1 Volume deficits are often present in trauma

patients and may result in the development of post-trauma

multiple organ failure on the intensive care unit (ICU). In addition to apparent blood loss, fluid deficits may

also occur secondary to generalized alterations of the endothelial barrier resulting in diffuse capillary

leakage and fluid shift from the intravascular to the interstitial compartment.

Adequate volume therapy appears to be a cornerstone of managing the trauma patient. In a prospective review of 111

consecutive patients who died in hospital after admission for treatment of injuries, the most common defects in patients

management were related to inadequate fluid resuscitation.2

Besides (hypo-, iso-, and hypertonic) crystalloids, human albumin (HA) and various synthetic colloids [e.g.,

dextrans, gelatins, hydroxyethyl starch (HES) preparations] are available to treat trauma-related volume deficits. In

recent years, the crystalloid/colloid dispute has been enlarged to a colloid/colloid debate because, aside from the natural

colloid albumin, several synthetic colloids are increasingly used as plasma substitutes in the trauma patient.

Aggressive pre-hospital fluid administration (in the field) has been common practice for more than 25 years in

trauma patients. Some recent studies, however, have shown that early volume restoration before definite hemostasis has

been performed may result in accelerated blood loss, hypothermia, and dilutional coagulopathy in certain types of

trauma.3 Thus it has been recommended that volume replacement should not be started early (concept of permissive

hypotension; scoop and run principle).4 This review is not designed to intensify the controversy between delayed

fluid resuscitation and early (field) volume replacement, nor to suggest new guidelines for appropriate volume therapy

in the trauma patient, but to recall the options for volume replacement and to analyze the literature according to

different volume replacement regimens in trauma patients exclusively. Trauma patients are definitely different from

cardiac surgery patients, patients with malignancies undergoing surgery or septic patients and thus volume replacementstrategies should be reviewed separately for these patients.

Pathophysiology of shock in the trauma patient Trauma is often associated with blood loss. Hemorrhage-related

hypovolemic shock after trauma can be divided into three phases:5

-phase I is the period from injury to operation for control of bleeding (pre-definitive care);

- phase II is the period during and immediately after the operation;

- phase III is the period in the ICU (post-definitive care).

Trauma-related hypovolemia may be associated with flow alterations which are inadequate to fulfill the nutritive role

of the circulation. Many of the manifestations of organ failure after successful primary resuscitation after trauma may

result from peripheral (micro-) circulatory derangements. In spite of achieving normal systemic hemodynamics it is

not guaranteed that perfusion in all organs and tissues is maintained as well. During low output syndrome the organismtries to compensate perfusion deficits by redistribution of flow to vital organs (e.g., heart, brain) resulting in an

underperfusion of other organs (splanchnic bed, kidney). Various inflammatory mediators and vasopressors are released

in this situation and are of particular importance for the development of impaired perfusion.

Recent evidence suggests that the endothelium is not only a passive barrier between the circulating blood and the

tissues, but may also be markedly involved in the regulation of microcirculatory blood flow by producing important

regulators of the vascular tone (e.g., prostaglandins, nitric oxide, endothelins, angiotensin II).6 The regional regulation

of blood flow is likely due to a balance between systemic mechanisms (e.g., the autonomous nervous system) and other

more locally active blood flow regulators. One important approach to improve perfusion in this situation appears to be

the use of adequate volume. Our pathophysiologic knowledge on the importance of the endothelium in modulating

microcirculation and inflammation has increased, however, the influence of different volume replacement strategies on

endothelial function has still to be elucidated.

Goals of volume replacement in the trauma patient The primary goal of volume administration is to guarantee stable

systemic hemodynamics and microcirculation by rapidly restoring circulating plasma volume. Excessive fluid

accumulation, particularly in the interstitial tissue should be avoided. Blood or blood products should be avoided as far

as possible due to unwanted risks.79

The infused fluid may stay in the intravascular compartment or equilibrate with the interstitial/intracellular fluid

compartments. Different mechanisms are involved in the control of volume and composition of each compartment

including the antidiuretic-hormone (ADH) system and the renin-angiotensin systems (RAS). The principal action of

these systems is to

T


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6% dextran 70 10% dextran

40Mean molecular weight 70,000 40,000

Volume effect (hr) 5 3-4

Volume efficacy (%) 100 175(200)

Maximum daily dose (gkg1) 1.5 1.5


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7 CANADIAN JOURNAL OF ANESTHESIA

Gelatins (Table II)Gelatins are modified beef collagens. Due to their low-

molecular weight (LMW) average (approximately 35 kD)

the intravascular half-life of gelatin infusions is short

(approximately two hours) and gelatins are supposed to

be the least effective colloids.16 This disadvantage is

balanced by the absence of a dose-limitation. Gelatins arelisted by the World Health Organization as an essential

drug. In the USA, however, gelatins were abandoned in

1978 due to a high incidence of hypersensitivity

reactions.17 Although the raw product is from beef,

gelatins are generally agreed to be free of risk of prion

transmission.18

HES (Table III)

HES is a high polymeric glucose compound that is

manufactured through hydrolysis and hydroxyethylation

from the highly branched starch amylopectin.

Polymerized D-glucose units are joined primarily by oneto four linkages with occasional one to six branching

linkages. The degree of branching is approximately 1:20,

which means that there is one to six branches for every

20 glucose monomer units. Natural starches cannot be

used as plasma substitutes because they are unstable and

rapidly hydrolyzed by circulating amylase. Substituting

hydroxyethyl for hydroxyl groups

TABLE II Characteristics of gelatin solutions

Urea-

crosslinked

Crosslinked Succinylatedgelatin gelatin

Concentration (%) 3.5 5.5 4.0

Meanmolecular

35,000 30,000 30,000

Volume effect (hr) 1-3 1-3 1-3

Volume efficacy 70-80 70-80 70-80

Osmolarit

y

301 296 274

results in a highly increased solubility and retards

hydrolysis of the compound by amylase, thereby delaying

its breakdown and elimination from the blood. The

hydroxyethyl groups are introduced mainly at carbon

position C2, C3, and C6 of the anhydroglucose

residues. The pharmacokinetics of HES preparations arefurther characterized by the pattern of

hydroxyethylation, in particular by the molar substitution

(MS) and by the degree of substitution (DS). The MS is

computed by counting the total number of hydroxyethyl

groups present and dividing the number by the quantity

of glucose molecules. The DS is determined by

measuring the number of substituted glucose molecules

and dividing this number by the total number of glucose

molecules present.

The available HES preparations are characterized by

concentration (low: 3%; medium: 6%; high: 10%), MS

(low: 0.4; medium: 0.5; high: 0.62 and 0.7), and the

mean-molecular weight [low-molecular weight (LMW)

HES: 70 kD; medium-molecular weight (MMW)- HES:

from 130 to 260 kD; high-molecular weight (HMW)-

HES: > 450 kD]. Current evidence indicates that the ratio

of the C2:C6 hydroxyethylation appears to be anotherimportant aspect for pharmacokinetic and side-effects

(e.g., accumulation, bleeding complications). Several

HES preparations are available commercially in Europe,

whereas in the USA only the first generation HMW-HES

(Hetastarch; concentration: 6%; Mw: 450 kD; MS: 0.7) is

approved for volume replacement, and in Canada only a

MMW-HES (HES 270/0.5; Pentastarch) was available

until recently.

Hypertonic solution (HS; Table IV)Enthusiasm has been expressed for HS or hypertonic-

hyperoncotic solutions in the treatment of hypovolemicshock in trauma patients. The concentration of sodium

ranges from 3% to 7.5% and HS appear to improve

cardiovascular function on multiple levels:


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Boldt: VOLUME REPLACE MENT IN TRAUMA PATIENTS 8

TABLE III Characteristics of different HES solutions

HES HES HES HES HES HES

70/0.5 130/0.4 200/0.5 200/0.5; 200/0.62 450/0.7

260/0.5 (Hetastarch)(Pentastarch

Concentration (%) 6 6 6 10 6 6

Volume efficacy (%) 80-90 100 100 130-150 100 100

Volume effect (hr) 1-2 3-4 3-4 3-4 5-6 5-6

Mean molecular weight (Mw) 70,000 130,000 200,000 200,000 200,000 450,000

(Daltons) 260,000

Degree of molar substitution (MS) 0.5 0.4 0.5 0.5 0.62 0.7

C2/C6 ratio 4:1 9:1 6:1 6:1 9:1 4.6:1

Max. dose (mLkg1) 33 33-50 33 20 33 20

HES = hydroxyethyl starch.


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TABLE IV Characteristics of hypertonic-colloid solutions

HyperHaesTM RescueFlowTM

(Fresenius, (BioPhausia,Germany) Sweden)

Electrolyte concentration 7.2% NaCl 7.5% NaCl

Sodium 1,232 mmolL1 1,283

mmolL

1

Osmolarity 2,464 mosmolL1 2,567

mosmolL1

Colloid hydroxyethyl starch dextran

Colloid concentration 6% 6%

Mean molecular 200 70

weight (kD)

Indication severe volume severe volume

deficit deficit

- displacement of tissue fluid into the blood com-

partment;

- direct vasodilatory effects in the systemic andpulmonary circulations;

- reduction in venous capacitance;

- and positive inotropic effects through direct actions

on myocardial cells.

The main mechanism of action of HS is the rapid

mobilization of endogenous fluid and subsequent plasma

volume expansion. Due to the hypertonicity of the

solutions, only a small volume of fluid (approximately 4

mLkg1) is necessary to effectively restore

cardiovascular function (small volume resuscitation).

The initial improvement in cardiovascular function (e.g.,

increase in cardiac output) seems to be mediated by the

hypertonicity of the solution, whereas the solute

composition does not seem to be important. Beneficial

effects of hypertonic saline solution were reported to be

rather transient. Thus, HS are often mixed with colloids

(dextran or HES), and these solutions show a significant

prolongation of efficacy. The use of extreme HS (up to

2,400 mosmolL1) has been studied in a limited number

of clinical trials, mostly in trauma patients with severe

hypovolemia and burns.

Clinical considerations of volume replacement in the

trauma patient

All fluids used for volume replacement in the trauma

patient have merits and demerits. The most alarming

problems that have to be considered when using a spe-

cific fluid are anaphylactoid reactions, increased bleeding

tendency, development of tissue edema, renal

dysfunction, and possible alterations of the immune

function.

Allergic reactionsThe use of crystalloids is not associated with anaphy-

lactic reactions. Dextran-associated anaphylactic reac-

tions are widely known for their frequency and severity.19

Gelatins are at risk of producing a larger number of

anaphylactic reactions compared with starch preparations

as shown in a large trial including approximately 20,000patients.20 Gelatins were associated more often with

severe, life-threatening anaphylactic reactions, whereas

this was very rare after the infusion of HES.20

Influence on coagulation and increasedbleeding tendency

Coagulopathy is a common complication of hemorrhagic

shock. Additionally, resuscitation-associated

hemodilution may alter hemostasis by lowering the

concentration of clotting proteins. Use ofcrystalloids has

been thought to be without negative influence oncoagulation except for that attributable to hemodilution,

although recent studies have demonstrated an increased

coagulability during hemodilution with saline.21 Albuminis considered to be the colloid with the least negative

influence on coagulation, although procoagulatory or

anticoagulatory effects (e.g., inhibiting platelet

aggregation, enhancing the inhibition of factor Xa by

antithrombin III) have been described with albumin.22

Dextrans are the plasma substitutes with the most widelyaccepted negative effects on hemostasis i.e., increasing

bleeding tendency. Using dextran both VIIIR:Ag and

VIIIR:RCo levels decrease significantly.23 With reduced

VIIIR:RCo there is a reduced binding to plateletmembrane receptor proteins GPIb and GPIIb/IIIa that

results in decreased platelet adhesion.23 Gelatins havebeen thought to possess no negative effect on

coagulation. However in a study in which healthy

humans received either 1,000 mL of gelatin or saline

solution, de Jonge et al.24 found that the infusion ofgelatin resulted in a significant impairment of primary

hemostasis and thrombin generation. Changes in

coagulation have most often been reported with the use of

HES.25 However, the different HES preparations have tobe distinguished concerning their influence on the hemo-

static process.26,27 HMW-HES (hetastarch) diminishes

concentrations of VIIIR:Ag and VIIIR:RCo more than aLMW-HES.23 Platelet aggregation abnormalities have

also been observed after the infusion of HMW-HES,

whereas infusion of HES with a LMW did not change

platelet aggregation induced by adenosine diphosphate.28

A substantial body of evidence supports the concept that

HES with MMWHES: 130 kD, 200 kD and especially

low MS (0.4;


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0.5) have significantly less negative effects on coagula-

tion and can be safely used with regard to hemostasis

in humans.27,28

Tissue edemaFactors contributing to tissue edema formation are

venous congestion, reduced COP, arteriolar vasodila-tion/venous vasoconstriction, disorganization of the

interstitial matrix, increased endothelial permeability, and

lymphatic dysfunction. COP appears to be an important

aspect in determining fluid shifts between the

intravascular and interstitial compartments. Manipulation

of COP appears to be promising to ensure adequate

intravascular volume. Controversy still exists whether the

choice of fluid for restoration of circulating volume is

able to limit development of tissue edema. Dilution of

serum proteins by the massive administration of

crystalloids lowers COP with the risk of progressive

expansion of the interstitial space. In a non-trauma

experimental peritonitis model, crystalloid infusionresulted in more pronounced endothelial cell swelling

and decreased systemic capillary cross-sectional area

compared with volume therapy with colloids.29

Maintenance of COP by the administration of albumin

has been postulated to be a desirable goal. The oncotic

force of concentrated albumin (e.g., HA 20%) has been

shown to reduce tissue edema (e.g., pulmonary edema). 30

In patients with impaired vascular endothelial integrity

(e.g., in trauma patients), albumin may pass into the

interstitial compartment and fluid will subsequently shift

from the intravascular to the interstitial space. A rapid

and profound increase in the transcapillary escape rate ofradio-labelled albumin has been described within six

hours of surgery.31 The endothelium may also swell and,

subsequently, microcirculatory perfusion is altered. In

severely ill patients it was shown that the addition of

albumin resulted in more signs of respiratory failure,

compared to patients who did not receive albumin. This

appears to be, most likely, due to increased leakage into

the interstitial space.32

In inflammatory-related capillary leaks, HES has been

reported to have occlusive effects on damaged

capillaries, subsequently limiting the extravasation of

fluid.33

LMW-HES may exert beneficial effects onendothelial function, e.g., by O2 free radical scavenging,

by stabilization of fragile cell membranes, or by avoiding

endothelial swelling. This may be of benefit, particularly

in those trauma patients suffering from severe endothelial

leakage syndrome.34

Renal functionRenal dysfunction in trauma patients may develop for

several reasons including insufficiently treated hypo-

volemia. Crystalloids have no specific negative effects on

renal function except that they may not restore blood

volume adequately. The effects of the different colloids

are controversial. In patients with excessive fluid deficits,

the glomerular filtration of hyperoncotic colloids

(dextrans, 10% HES, 20% or 25% albumin) causes a

hyperviscous urine and stasis of the tubular flow resulting

in obstruction of tubular lumen.35

Certain commerciallyavailable albumins are known to contain remarkable

quantities of ions from the preparation process resulting

in toxic concentrations of aluminium in patients with

acute renal failure.36 HES molecules and gelatin

molecules are eliminated by glomerular filtration.

Gelatins appear to be almost devoid of significant

damaging effects on the kidneys. In a retrospective

analysis of patients undergoing kidney transplantation

and in whom HES with a high DS (0.62) was infused,

osmotic-nephrosis-like lesions were documented.37

This phenomenon, however, did not have negative effects

on graft function three and six months after

transplantation. Use of 6% HES 200/0.62 (2,100 660mL) in brain-dead donors resulted in impaired renal

function in kidney transplant recipients.38 Patients treated

with this HES preparation with a high MS showed higher

serum creatinine concentrations and a more frequent need

for hemodialysis compared to a gelatin-treated group of

patients. In a multicentre study in intensive care patients,

HES (200/0.62) resulted in a significantly higher

incidence of renal failure compared to a comparable

group of patients who received a gelatin preparation.39

Fortunately, the authors distinguished between different

types of starches, and state that the results of the study

may not be applicable to more rapidly degradable HES

preparations (e.g., HES 200/0.5). Use of HES 200/0.5over five days in a study of critically ill ICU patients was

without negative effects on renal function compared to a

control group in whom albumin was administered. 40 In a

study in elderly patients (> 75 yr) administration of 6%

HES 200/0.5 undergoing major abdominal surgery was

not associated with relevant changes of markers of renal

function (e.g., alpha-1-microglobulin, N-acetylbeta-D-

glucosaminidase).41

Accumulation and dose limitationsStoring, accumulation, and dose limitations have to beconsidered only when using synthetic colloids. Gelatin

and dextrans are naturally occurring substances and both

are fully metabolized in man. Nevertheless, a dose-

limitation exists for dextrans (approximately 2,500

mLday1) most likely because higher doses are

associated with severe bleeding complications. All


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available HES preparations are stored and may accu-

mulate depending on the preparation. The smaller

molecules are rapidly eliminated by glomerular filtration.

A varying proportion of the HES administered leaves the

vascular space and is taken up by the reticuloendothelial

system (RES). RES storage, however, appears to be

without detrimental consequences.42

Nevertheless, a doselimitation exists for all HES preparations ranging from 20

mLkg1 to 50 mLkg1.

Immune function

Traumatic injury is known to induce intense alterations in

circulatory hemostasis and cell-mediated or humoral

immunity.43 These sequelae of trauma predispose to the

development of post-trauma sepsis or systemic

inflammatory response syndrome (SIRS). The mediators

of immunosuppression secondary to trauma are not

definitely elucidated. Endotoxin, tissue metabolicproducts resulting from cellular hypoxia, shock proteins,

hormonal mediators (e.g., catecholamines) are suspected

to take part in this process. Polymorphonuclear cells are

supposed to be key mediators of tissue injury and organ

failure. While neutrophils are essential for bacterial

killing, they paradoxically have the capacity to injure

host tissue. The interactions of neutrophils with

endothelial cells are regulated by complementary

adhesion molecules, which are present on these cells

(e.g., the immunoglobulin superfamily [e.g., vascular cell

adhesion molecule-1 (VCAM-1), intercellular adhesion

molecule-1 (ICAM-1)]; the integrin family [e.g., lym-

phocyte function-associated antigen (e.g., LFA-1 =CD11a/CD18)]; the selectins [E-selectin = endothelial

leukocyte adhesion molecule (ELAM-1)]; Lselectin =

e.g., leukocyte endothelial cell adhesion molecule; P-

selectin = granule membrane protein 140 (= GMP-140).

The soluble forms of some of these adhesion molecules

appear to be excellent markers of inflammation and

endothelial activation or damage.44The influence of HES

on endothelial cell activation was studied experimentally

by Collis et al.45 using endothelial cell cultures (humanumbilical vein endothelial cells ). E-selectin expression

on lipopolysaccharide-stimulated endothelial cells was

not influenced by HES. The authors, however, suggested

a possible beneficial role of HES by inhibitingendothelial activation. Thrombin-stimulated von

Willebrand factor (vWF) release was significantly more

reduced in the presence of HES than in the presence of

HA. The authors concluded from their data that HES may

be able to inhibit endothelial activation with subsequent

damage of endothelial integrity and that, by this

mechanism, HES may be able to ameliorate

capillary leak secondary to inflammation. The effects of

10% HES 200/0.5 or 20% albumin for volume

replacement over five days in severely (non-septic)

traumatized patients on plasma levels of circulating

adhesion molecules were assessed in a prospective ran-

domized study.46 Soluble ELAM- 1, soluble ICAM- 1,

and soluble VCAM- 1 plasma levels did not differ

between HES- and HA-treated patients indicating no

negative effect of the synthetic colloid HES on

endothelial function.

Volume replacement in trauma patient: analysis of the

literature

In the Advanced Trauma Life Support guidelinesRingers lactate is recommended as part of the emer-

gency resuscitation of the trauma patient, proceeding to

blood products as required.47 The American College of

Surgeons Classes of Acute Hemorrhages specify fourclasses of acute hemorrhage using a blood loss ranging

from up to 750 mL to > 2,000 mL.48 Fluid replacement

should be performed with crystalloids exclusively (3:1

rule) - there is no place for infusing (synthetic) colloids in

their recommendations.

Analysis of the literature

Crystalloids vs colloids in trauma patients

PUBLISHED META-ANALYSES

We are living in times of meta-analyses and evidence

based medicine (EBM). Different volume replacement

regimens have been examined with the help of these

popular instruments:

- In a meta-analysis from 1989, a possible reduction in

mortality was documented when crystalloids were used in

traumatized patients.49 In this analysis, five trauma

studies were included, two were from 1981, one from

1979, one from 1978, and one from 1977.

- In a meta-analysis by Schierhout and Robertson in

1998,50 the use of colloids was associated with an

increased incidence of death. Seven trauma studies were

included in this meta-analysis - three of them used

hypertonic/colloidal solutions, two albumin, one dextran,

and another gelatin. Summarizing all 37 analyzed studies,

resuscitation with colloids was associated with an

increased absolute risk of mortality of 4% (or four extra

deaths for every 100 patients resuscitated).

- In the Cochrane EBM analysis on volume

replacement in 1998, four trauma studies were included -one was from 1977, two were from 1978, and one was

from 1983.51 The message of this EBM analysis was that

albumin kills our patients (for every 17 patients treated

with albumin there was one additional death).


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TABLE V Volume replacement in adult trauma patients: crystalloid/colloid controversy

Author/year Substance Pro/retro Area Kind of Aim Conclusion

(reference) no. of patients rand/d-b trauma

Modig dextran 70 n = 14 pro/rand post only over seven days dex: better hemodynamics;

1986 (56) crystalloids (RA) n = 17 trauma severe dex:0.5l renal, coagulation: no differences

ICU factures RA:1.0-1.5l outcome: no differences

Nagy HES 250 (PS) n = 21 pro/rand E blunt maintain hemostasis: no differences

1993 (57) crystalloids (RL) n = 20 penetr. hemodynamic renal system: no differences

stability outcome: no differences

Sinclair crystalloids n = 20 pro/rand OR proximal replace HES: more effective1997 (58) cryst + HES n = 20 femoral blood loss HES: reduced hospital stay

fracture outcome: no differences

Evans gelatin (H) n = 19 pro/rand E blunt ? gelatin: increased Ca++ levels

1997 (59) crystalloids n = 5 outcome: not shown

Younes HES 250 (PS) n = 12 pro/rand E blunt SBP hemodynamics: no differences1998 (60) crystalloids (NS) n = 11 penetr. >100 mmHg transfusion: no differences

stab 24 hr survival: similar

Wu gelatin n = 18 pros/rand E ? fixed dose gelatin: better hemodynamics

2001 (61) RL n = 16 1000 mL outcome: no differences

PS = pentastarch; RL = Ringers lactate; RA = Ringers acetate; NS = 0.9% NaCl; HA = human albumin; kD = kilo Daltons;E = emergency room; OR = operating room; H = Haemaccel; F = in the f ield; ICU = intensive care unit; pro = prospectively;

rand = randomized; blunt = blunt trauma; penetr. = penetrating trauma; SBP = systolic blood pressure; dex = dextran; HES =

hydroxethyl starch; d-b = double-blind.


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- Only one meta-analysis distinguished between

trauma patients and other kinds of patients (e.g., cardiac

surgery, critical care patients).52 In this analysis from

1999 four trauma studies were included; all of them

were more than 17 years old. All kinds of colloids

were compared to crystalloid-based resuscitation. There

were no differences between the two volumereplacement strategies.

- The influence of an albumin-based volume therapy

on mortality compared to other less expensive volume

replacement strategies was compared in a meta-analysis

of randomized controlled trials in 2001.53 No study more

recent than 2000 was included. In one subgroup, studies

involving surgery and trauma (27 studies) were included.

None of the analyzed factors (outcome, mortality) were

significantly influenced by either volume replacement

regimens. There was, overall, no beneficial effect of

(expensive) albumin in comparison to other (cheaper)

plasma substitutes on mortality.

Meta-analyses have two fundamental problems:54

1)There may be a selection bias of included trials; and

2)the results of the analyses may be similar, but theycan be interpreted quite differently. Specific objections to

all meta-analyses on volume therapy are:

- The mixing of patients with different diseases;

- The use of different kinds of fluids that have been

infused;

- The physicochemical properties of the various

synthetic colloids have been neglected in all meta-

analyses. Because of the important differences between

individual colloids, it is not appropriate to summarize allcolloids in a colloid group.

- Most meta-analyses include studies more than 15

years old. Important innovative strategies have been

developed in managing the trauma patient in the last 15

years including improved monitoring techniques,

ventilation strategies, feeding, and others that may also

influence outcomes.

- Mortality was used as the endpoint for volume

replacement in all meta-analyses. However, mortality was

not the endpoint of most of the volume replacement

studies. None of the studies found a statistically

significant effect that favoured colloids. It is still unclear

whether mortality is helpful to determine the optimalvolume resuscitation strategy.55

Description of primary studiesWith the help of a MEDLINE search, recent studies

dealing with volume therapy in trauma patients were


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Boldt: VOLUME REPLAC EMENT IN TRAUM A PATIENTS 14

TABLE VI Volume replacement in adult tr auma patients: colloid/colloid controversy

Auth

/year

Substance

no. of patients

Pro/retro

rand/d-b

Area Kind

of

Aim

Boldt 10% HES 200 n = 15 pro/rand post blunt CVP

1995 (62) 20% HA n = 15 traum

a

penetr. 12-16

Boldt 10% HES 200/0.5 n = 15 pro/rand post- blunt PCWP

1996 (63) 20% albumin (n = 15) traum penetr. 10-15

ICU

Boldt 10% HES 200 n = 15 pro/rand post blunt CVP/PCW

1996 (46) 20% HA n = 15 trau

maIC

penetr. 12-

18mm

Boldt 10% HES 200 n = 15 pro/rand post blunt PCWP

1996 (64) 20% HA n = 15 trau

ma

penetr. 12-

18

Boldt 10% HES 200 n = 14 pro/rand post blunt CVP/PCW

1996 (28) 20% HA n = 14 trau

ma

penetr. 12-

16

Boldt 10% HES 200 n = 75 pro/rand post blunt PCWP

1998 (28) 20% HA n = 75 trau

maIC

penetr. 12-

15mm

Allison1999 (65)

HES 250/0.45 (PS) n = 24

gelatin n = 21

pro/rand E blunt ?

Conclusion

(endothelial) coagulation: no differences

outcome: no differences

albumin: lower CI and pHi HES: beneficial effects on regulators of circulation outcome: no differences

HES: lower levels of adhesion molecules than HA


HES: better hemodynamics HES: better VO2 and VO2outcome: no differences

platelet function: no differences blood use: no differences outcome: no differences

HES: better hemodynamics HES: no side-effects


HES: reduced capillary leak renal/blood use: no differences outcome: not shown


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PS = pentastarch; RL = Ringers lactate ; RA = Ringers acetate; NS = 0.9% NaCl; HA = human albumin; kD = kilo Daltons;

E = emergency room; OR = operating room; F = in the field; ICU = intensive care unit; pro = prospectively; rand = randomized;

blunt = blunt trauma; penetr. = penetrating trauma; HES = hydroxethyl starch; d-b = double-blind; pts = patients; CVP = central

venous pressure; PCWP = pulmonary capillary wedge pressure; CI = confidence interval; pHi = gastric intramucosal pH.


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identified. Only studies published in English in

adult patients on pre-hospital volume

replacement, volume replacement in the

emergency area or in the operating room (OR), and

volume therapy in the trauma ICU published in theperiod from January 1st 1985 to December 31st

2002 were included. Studies in head trauma

patients, in traumatized children, and in burned

trauma patients were not included. Only original

studies comparing different solutions for volume

therapy were analyzed. Published abstracts,

reviews, and letters were not included. Animal or

experimental studies were excluded because

animal models cannot completely mimic thehuman trauma situation.

A total of 13 studies were found and analyzed:

six of them compared a crystalloid- vs a colloid-

based volume replacement regimen5661

(Table V)and seven compared different colloids for volume

resuscitation28,40,46,6265 (Table VI). In none of the

studies were different volume regimens during

primary resuscita tion (in the field) studied. In six

studies different volumes were administered in the

emergency department (E) or in the OR,5761,65 and

another seven studies looked at different volume

therapies in the post- surgery period in theICU.28,40,46,56,6264 The study population in eachvolume group of the different studies differed

widely, ranging from five to 75 patients. The

amount of volume administered also differed

widely (from 500 to > 3,500 mL) or was not

mentioned.

Limitations of existing studies

GOALS FOR VOLUME THERAPY

What goals of volume therapy were used in the

studies to guide specific volume replacement?

Unfortunately, standardized protocols were used

only in a few studies. Volume replacement wasadapted with regard to hemodynamic data [tomaintain filling pressures e.g., central venous

pressure, pulmonary


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capillary wedge pressure (PCWP), to keep systolic

blood pressure > 100 mmHg]. Other studies only used

fixed doses of the different solutions without use of a

specific protocol.

ENDPOINTS TO ASSESS THE EFFICACY OF VOLUME THERAPY

Most studies were not focused primarily on outcome andoutcome was not reported in some studies. Thus the

influence of different volume replacement regimens on

outcome in trauma patients cannot be determined by the

studies examined.

Some studies focused only on possible adverse events

(e.g., hemostasis, kidney/pulmonary function,

inflammation). Because coagulation abnormalities have

been reported, especially after the administration of HES,

some studies looked especially at alterations of

hemostasis after infusion ofHES.28,56,57,62 The general result

from these studies was that the use of modern HES

preparations is not associated with impaired hemostasis

or an increased bleeding tendency.

One study focused on capillary leakage.65 In 45

patients suffering from blunt trauma either HES [Mw 250

kD (PentaspanTM, Bristol-Myers Squibb, Montreal, Qc,

Canada)] or gelatin were given for the first 24 hr.

Resuscitation with HES resulted in significantly less

post-trauma capillary leak (measured by

microalbuminuria) than resuscitation with gelatin.

DURATION OF VOLUME THERAPY

Unfortunately, some trials only compared rather short-

term effects of different volume replacement strategies.At the end of the study period, no further strict infusion

protocols were implemented. A definitive evaluation of

the efficacy of different volume replacement regimens is

not possible with such a design. In a prospective ran-

domized study, long-term volume therapy using either

20% HA or 6% HES 200/0.5 in the ICU was studied in

trauma patients with an Injury Severity Score > 15

points.63 HA or HES exclusively were infused over five

days to keep PCWP between 10 and 15 mmHg. Besides

hemodynamic monitoring, liver function was assessed

using the monoethylglycinexylidide test. Gastric

intramucosal pH was monitored by tonometry to evaluate

splanchnic perfusion. Additionally, important regulatorsof circulation were measured from arterial blood samples.

Mean arterial pressure, heart rate, and PCWP did not

differ between the two groups, whereas confidence

interval increased significantly more in the HES than in

the HA group. Liver function and splanchnic perfusion

were also similar between HA- and HES-treated trauma

patients. Concentrations of all vasoactive regulators

showed an almost similar course in

both groups. Thus, in trauma patients, long-term volume

therapy with HA did not show any advantages over a

modern HES solution.

Volume replacement with HS

Treatment of trauma-related hypovolemia using

hypertonic (and hyperoncotic) solutions should beassessed separately from the classic colloid/crystalloid

or colloid/colloid debate because this represents a special

issue. This strategy is mostly used in the early (field)

resuscitation of hemorrhagic hypovolemia.

PUBLISHED META-ANALYSES- In a meta-analysis of the efficacy of a hypertonic

7.5% saline/6% dextran solution in trauma patients from

1997, nine (original) studies were analyzed.66 The

analysis revealed no significant improvement in outcome

after the infusion of hypertonic saline solution, whereas

the use of hypertonic saline plus dextran (HSD) may be

superior compared to isotonic fluid resuscitation.

- In a recently published meta-analysis (Cochrane

review) from 2002, the use of crystalloids was compared

with HS. Five studies in trauma patients were included.

No beneficial influence of HS on outcome was found.67

MEDLINE-ANALYSIS

In our MEDLINE analysis on HS, 12 studies were found

and analyzed (Table VII, available as Additional Material

at www.cja-jca.org).6877 Either hypertonic saline solution

(HS; 7.5% NaCl) or a combination of HS with colloid

(6% dextran 70; HSD) were used (Table IV). All studies

used crystalloids [mostly normal saline solution (NS)] asa control group. The use of colloids was not compared.

Six studies used HS in the field, five in the E, and one in

the OR. Patient populations ranged from seven to 211

patients per group. The studies analyzed have several

problems.

GOALS AND ENDPOINTS FOR VOLUME THERAPY

In most of the studies analyzed, a fixed volume of either

fluid was given (250 mL). It is doubtful that 250 mL of

an isotonic crystalloid (e.g., NS) was adequate to treat

hypovolemia in trauma patients in the control groups.

Systemic hemodynamics were either improved or withoutdifferences compared to the use of crystalloids. No

negative influence on hemostasis, bleeding or use of

packed red cells was documented. Outcome was not

affected beneficially by the use of a hypertonic volume

replacement strategy.

ConclusionsIn the severely hypovolemic trauma patient adequate

volume restoration appears to be essential to treat non-

compensatory, irreversible shock. Lengthy uncorrected

hypovolemia will jeopardize survival by the continuous
http://www.cja-jca.org/http://www.cja-jca.org/


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stimulation of various vasopressive and immune

cascades. Prolonged under-resuscitation of the

hypovolemic trauma patient may have fatal consequences

for organ function. Thus, vigorous optimization of the

circulation - at least when surgical hemostasis has been

achieved - is a prerequisite to avoid development of

multiple organ dysfunction syndrome in the traumapatient. 78 This maneuver is aimed at assuring stable

macro- and microhemodynamics while avoiding

excessive fluid accumulation in the interstitial tissue.

Blood volume is restored more rapidly with colloids than

with crystalloids, colloids are more efficient resuscitative

fluids than crystalloids,79 and colloids are a more efficient

regimen to ensure adequate microcirculatory flow than

crystalloids.11,80 Especially hypotonic solutions (e.g.,

Ringers lactate, hypotonic colloids) should be avoided

due to the risk of (interstitial) fluid overload. Use of

balanced colloids is a promising alternative to avoid

electrolyte imbalances and overflow into the interstitial

compartment in this situation.

What endpoints should be chosen to assess the ideal

volume replacement strategy? Although often used,

clinical signs of hypovolemia are non-specific and

insensitive. Most studies on volume replacement in

trauma patients were not focused on outcome. It remains

unclear whether mortality is an appropriate endpoint

when comparing different volume replacement

strategies.55 New concepts on trauma, the development of

SIRS, and post-trauma organ dysfunction (e.g., renal or

pulmonary insufficiency) should change this point of

view.

Very few studies are available comparing different

volume replacement protocols exclusively in trauma

patients. Based on these limited data, the publication of

strict recommendations on the best volume

replacement strategy in the hypovolemic trauma patient

comes as a surprise. Further studies are necessary to

distinguish different types (e.g., with/without head injury,

blunt trauma, penetrating trauma) and severity of trauma.

We should not only consider young, strong male victims

but also - especially in highly industrialized countries -

the > 70-yr-old trauma patient who presents with several

comorbid states. It is time to leave emotions aside when

discussing the most appropriate volume replacement

strategy in trauma patients and to concentrate on the

available scientific evidence. We need improved

monitoring technologies that will help us guide volume

therapy and better point-of-care markers that will help

us assess when volume therapy is appropriate in the trau-

ma patient.

References

1 MacKenzie EJ, Morris JA Jr, Smith GS, Fahey M. Acute

hospital costs of trauma in the United States: implications

for regionalized systems of care. J Trauma 1990; 30: 1096

103.

2 Deane SA, Gaudry PL, Woods P, et al. The managment of

injuries - a review of deaths in hospital. Aust N Z J Surg

1988; 58: 4639.

3Deakin CD. Early fluid resuscitation in haemorrhagic

shock. Eur J Emerg Med 1994; 1: 835.

4Bickell WH. Are victims of injury sometimes victimized by

attempts at fluid resuscitation? Ann Emerg Med 1993; 22:

2256.

5Lucas CE. Update on trauma in Canada. 4. Resuscitation

through the three phases of hemorrhagic shock after

trauma. Can J Surg 1990; 33: 45 16.

6 Vane JR, Anggard EE, Botting RM. Regulatory functions of

the vascular endothelium. N Engl J Med 1990; 323: 2736.

7 Hebert PC, Wells G, Blajchman MA, et al. A multicenter,

randomized, controlled clinical trial of transfusion

requirements in critical care. Transfusion requirements in

critical care investigators, and the Canadian Critical CareTrials Group. N Engl J Med 1999; 340: 40917.

8Landers DF, Hill GE, Wong KC, Fox IJ. Blood transfusion-

induced immunomodulation. Anesth Analg 1996; 82: 187

204.

9 Agarwal 1V, Murphy JG, Cayten CG, Stahl WM. Blood

transfusion increases the risk of infection after trauma.

Arch Surg 1993; 128: 1717.

10 Vaupshas HJ, Levy M. Distribution of saline following acute

volume loading: postural effects. Clin Invest Med 1990; 13:

16577.

11 Funk W, Baldinger V. Microcirculatory perfusion during

volume therapy. A comparative study using crystalloid or

colloid in awake animals. Anesthesiology 1995; 82: 97582.

12Prien T, Backhaus 1V, Pelster F, Pircher W, Bunte H, Lawin

P. Effect of intraoperative fluid administration and colloid

osmotic pressure on the formation of intestinal edema

during gastrointestinal surgery. J Clin Anesth 1990; 2:

31723.

13 Schott U, Lindbom LO, Sjostrand U. Hemodynamic effects

of colloid concentration in experimental hemorrhage: a

comparison of Ringers acetate, 3% dextran-60 and 6%

dextran-70. Crit Care Med 1988; 16: 34652.

14Margarson MP, Soni 1V. Serum albumin: touchstone or

totem? Anaesthesia 1998; 53: 789803.


19/21


15 Qiao R, Siflinger-Birnboim A, Lum H, Tiruppathi C,

Malik AB. Albumin and ricinus communis agglutinin

decrease endothelial permeability via interactions with

matrix. Am J Physiol 1993; 265(2 Pt 1): C43946.

16 Kreimeier U, Peter K. Strategies of volume therapy in

sepsis and systemic inflammatory response syndrome.

Kidney Int Suppl 1998; 64: S759.17Nearman HS, Herman ML. Toxic effects of colloids in the

intensive care unit. Crit Care Clin 1991; 7: 71323.

18Peano S, Reiner G, Carbonatto M, Bodenbender L,

Boland P, Abel KJ. Determination of the clearance factor

for transmissible spongiform encephalopathy agents during

the manufacturing process of polygeline. Intensive Care

Med 2000; 26: 60812.

19Paull J. A prospective study of dextran-induced ana-

phylactoid reactions in 5745 patients. Anaesth Intensive

Care 1987; 15: 1637.

20Laxenaire MC, Charpentier C, Feldman L. Anaphylactoid

reactions to colloid plasma substitutes: incidence, risk

factors, mechanisms. A French multicenter prospective

study (French). Ann Fr Anesth Reanim 1994; 13: 30110.

21Ruttmann TG, James MF, Aronson I. In vivo investigation

into the effects of haemodilution with hydroxyethyl starch

(200/0.5) and normal saline on coagulation. Br J Anaesth

1998; 80: 6126.

22Joorgensen KA, Stoffersen E. Heparin like activity of

albumin. Thromb Res 1979; 16: 6974.

23 Strauss RG. Volume replacement and coagulation: a

comparative review. J Cardiothorac Anesth 1988;

2(suppl 1): 2432.

24 de Jonge E, Levi M, Berends F, van der Ende AE, ten

Cate JW, Stoutenbeek CP. Impaired haemostasis byintravenous administration of a gelatin-based plasma

expander in human subjects. Thromb Haemost 1998; 79:

28690.

25 Warren BB, Durieux ME. Hydroxyethyl starch: safe or

not? Anesth Analg 1997; 84: 20612.

26 Treib J, Haass A, Pindur G, Grauer MT, Wenzel E,

Schimrigk K. All medium starches are not the same:

influence of the degree of hydroxyethyl substitution of

hydroxyethyl starch on plasma volume, hemorrheologic

conditions, and coagulation. Transfusion 1996; 36: 4505.

27 de Jonge E, Levi M. Effects of different plasma substitutes

on blood coagulation: a comparative review. Crit Care

Med 2001; 29: 12617.

28Boldt J, Muller M, Heesen M, Heyn O, Hempelmann G.

Influence of different volume therapies on platelet function

in the critically ill. Intensive Care Med 1996; 22: 107581.

29Morisaki H, Bloos F, Keys J, Martin C, Neal A, Sibbald

WJ. Compared with crystalloid, colloid therapy slows

progression of extrapulmonary tissue injury in septic

sheep. J Appl Physiol 1994; 77: 150718.

30 Weil MH, Henning RJ, Puri VK. Colloid oncotic pressure:

clinical significance. Crit Care Med 1979; 7: 11326.

31Fleck A, Raines G, Hawker F, et al. Increased vascular

permeability: a major cause of hypoalbuminaemia in

disease and injury. Lancet 1985; 1: 7814.

32Rackow EC, Mecher C, Astiz ME, Griffel M, Falk JL,

Weil MH. Effects of pentastarch and albumin infusion on

cardiorespiratory function and coagulation in patients with

severe sepsis and systemic hypoperfusion. Crit Care Med1989; 17: 3948.

33 Vincent JL. Plugging the leaks? New insights into synthetic

colloids. Crit Care Med 1991; 19: 3168.

34 Gosling P, Sanghera K, Dickson G. Generalized vascular

permeability and pulmonary function in patients following

serious trauma. J Trauma 1994; 36: 47781.

35 Rozich JD, Paul RV. Acute renal failure precipitated by

elevated colloid osmotic pressure. Am J Med 1989; 87:

35960.

36Koppel C, Baudisch H, Ibe K. Inadvertent metal loading

of critically ill patients with acute renal failure by human

albumin solution infusion therapy. J Toxicol Clin Toxicol

1988; 26: 33756.

37Legendre C, Thervet E, Page B, Percheron A, Noel LH,

Kreis H. Hydroxyethylstarch and osmotic-nephrosislike

lesions in kidney transplantation. Lancet 1993; 342: 248

9.

38 Cittanova ML, Leblanc I, Legendre C, Mouquet C, Riou

B, Coriat P. Effect of hydroxyethylstarch in brain-dead

kidney donors on renal function in kidney-transplant

recipients. Lancet 1996; 348: 16202.

39 Schortgen F, Lacherade JC, Bruneel F, et al. Effects of

hydroxyethylstarch and gelatin on renal function in severe

sepsis: a multicentre randomised study. Lancet 2001; 357:

9116.40Boldt J, Mller M, Mentges D, Papsdorf M,

Hempelmann G. Volume therapy in the critically ill: is

there a difference? Intensive Care Med 1998; 24: 2836.

41Kumle B, Boldt J, Piper S, Schmidt C, Suttner S, Salopek

S. The influence of different intravascular volume

replacement regimens on renal function in the elderly.

Anesth Analg 1999; 89: 112430.

42 Shatney CH, Chaudry IH. Hydroxethylstarch adminis-

tration does not depress reticuloendothelial function or

increase mortality from sepsis. Circ Shock 1994; 13: 216.

43Dorman T, Breslow MJ. Altered immune function after

trauma and hemorrhage: what does it all mean? Crit Care

Med 1994; 22: 106970.


20/21


44 Seth R, Raymond FD, Makgoba MW. Circulating

ICAM-1 isoforms: diagnostic prospects for inflammatory

and immune disorders. Lancet 1991; 338: 834.

45 Collis RE, Collins PW, Gutteridge CN, et al. The effect of

hydroxyethyl starch and other plasma volume substitutes on

endothelial cell activation: an in vitro study. Intensive Care

Med 1994; 20: 3741.46Boldt J, Muller M, Heesen M, Neumann K,

Hempelmann GG. Influence of different volume therapies

and pentoxifylline infusion on circulating soluble adhesion

molecules in critically ill patients. Crit Care Med 1996; 24:

38591.

47Bell RM, Krantz BE, Weigelt JA. ATLS: a foundation for

trauma training. Ann Emerg Med 1999; 34: 2337.

48Miller RD. Update on blood transfusions and blood

substitutes. Anest Analg 1999; 88(suppl): 718.

49 Velanovich V. Crystalloid versus colloid fluid resuscitation:

a meta-analysis of mortality. Surgery 1989; 105: 6571.

50 Schierhout G, Roberts I. Fluid resuscitation with colloid or

crystalloid solutions in critically ill patients: a systematic

review of randomised trials. BMJ 1998; 316: 9614.

51Anonymous. Human albumin administration in critically ill

patients: systematic review of randomised controlled trials.

Cochrane Injuries Group Albumin Reviewers. BMJ 1998;

317: 23540.

52 Choi PT, Yip G, Quinonez LG, Cook DJ. Crystalloids vs.

colloids in fluid resuscitation: a systematic review. Crit

Care Med 1999; 27: 20010.

53 Wilkes MM, Navickis RJ. Patient survival after human

albumin administration. A meta-analysis of randomized,

controlled trials. Ann Intern Med 2001; 135: 14964.

54 Cook D, Guyatt G. Colloid use for fluid resuscitation:evidence and spin. Ann Intern Med 2001; 135: 2058.

55Astiz ME, Rackow EC. Crystalloid-colloid controversy

revisited. Crit Care Med 1999; 27: 345.

56Modig J. Effectiveness of dextran 70 versus Ringers acetate

in traumatic shock and adult respiratory distress syndrome.

Crit Care Med 1986; 14: 4547.

57Nagy KK, Davis J, Duda J, Fildes J, Roberts R, Barrett J.

A comparison of pentastarch and lactated Ringers solution

in the resuscitation of patients with hemorrhagic shock. Circ

Shock 1993; 40: 28994.

58 Sinclair S, James S, Singer M. Intraoperative intravascular

volume optimisation and length of hospital stay after repair

of proximal femoral fracture: randomised controlled trial.

BMJ 1997; 315: 90912.

59Evans PA, Madira W, Riyatt MS, Errington M,

Heptinstall S. Changes in plasma ionised calcium within

24 hours of trauma in patients infused with the calcium

containing colloid Haemaccel during fluid

resuscitation. J Accid Emerg Med 1997; 14: 735.

60 Younes RN, Yin KC, Amino CJ, Itinoshe M, Roca e Silva

M, Birolini D. Use of pentastarch solution in the treatment

of patients with hemorrhagic hypovolemia: randomized

phase II study in the emergency room. World J Surg 1998;

22: 25.

61 Wu JJ, Huang MS, Tang GJ, et al. Hemodynamic

response of modified fluid gelatin compared with lactated

ringers solution for volume expansion in emergency

resuscitation of hypovolemic shock patients: preliminary

report of a prospective, randomized trial. World J Surg2001; 25: 598602.

62Boldt J, Heesen M, Welters I, Padberg W, Martin K,

Hempelmann G. Does the type of volume therapy

influence endothelial-related coagulation in the critically

ill? Br J Anaesth 1995; 75: 7406.

63Boldt J, Muller M, Menges T, Papsd orf M, Hemp elmann

G. Influence of different volume therapy regimens on

regulators of the circulation in the critically ill. Br J

Anaesth 1996; 77: 4807.

64Boldt J, Heesen M, Muller M, Pabsd orf M, Hemp

elmann G. The effects of albumin versus hydroxyethyl

starch solution on cardiorespiratory and circulatory

variables in critically ill patients. Anesth Analg 1996; 83:

25461.

65Allison KP, Gosling P, Jones S, Pallister I, Porter KM.

Randomized trial of hydroxyethyl starch versus gelatine for

trauma resuscitation. J Trauma 1999; 47: 111421.

66 Wade CE, Kramer GC, Grady JJ, Fabian TC, Younes RN.

Efficacy of hypertonic 7.5% saline and 6% dextran70 in

treating trauma: a meta-analysis of controlled clinical

studies. Surgery 1997; 122: 60916.

67Bunn F, Roberts I, Tasker R, Akpa E. Hypertonic versus

isotonic crystalloid for fluid resuscitation in critically ill

patients. Cochrane Database Syst Rev 2002; CD002045.

68Holcroft JW, Vassar MJ, Turner JE, Derlet RW, KramerGC. 3% NaCl and 7.5% NaCl/dextran 70 in the resus-

citation of severely injured patients. Ann Surg 1987; 206:

27988.

69Holcroft JW, Vassar MJ, Perry CA, Gannaway WL,

Kramer GC. Use of 7.5% NaCL/6% Dextran 70 solution in

the resuscitation of injured patients in the emergency room.

Prog Clin Biol Res 1989; 299: 3318.

70Maningas PA, Mattox KL, Pepe PE, Jones RL, Feliciano

DV, Burch JM. Hypertonic saline-dextran solutions for the

prehospital management of traumatic hypotension. Am J

Surg 1989; 157: 52833.

71 Vassar MJ, Perry CA, Holcroft JW. Analysis of potential

risks associated with 7.5% sodium chloride resuscitation of

traumatic shock. Arch Surg 1990; 125: 130915.

72 Mattox KL, Maningas PA, Moore EE, et al. Prehospital

hypertonic saline/dextran infusion for post-traumatic


21/21


hypotension. The U.S.A. Multicenter Trial. Ann Surg

1991; 213: 48291.

73 Vassar MJ, Perry CA, Gannaway WL, Holcroft JW.7.5% sodium chloride/dextran for resuscitation of trauma

patients undergoing helicopter transport. Arch Surg 1991;

126: 106572.

74 Younes RN, Aun F, Accioly CQ, Casale LP, Szajnbok I,

Birolini D. Hypertonic solutions in the treatment ofhypovolemic shock: a prospective, randomized study in

patients admitted to the emergency room. Surgery 1992;

111: 3805.

75 Vassar MJ, Perry CA, Holcroft JW. Prehospital resusci-

tation of hypotensive trauma patients with 7.5% NaCl

versus 7.5% NaCl with added dextran: a controlled trial. J

Trauma 1993; 34: 62232.

76 Vassar MJ, Fischer RP, OBrien PE, et al. A multicenter

trial for resuscitation of injured patients with 7.5% sodium

chloride. The effect of added dextran 70. Arch Surg 1993;

128: 100311.

77 Younes RN, Aun F, Ching CT, et al. Prognostic factors topredict outcome following the administration of

hypertonic/hyperoncotic solution in hypovolemic patients.

Shock 1997; 7: 7983.

78 de Guzman E, Shankar MN, Mattox KL. Limited volume

resuscitation in penetrating thoracoabdominal trauma.

AACN Clin Issues 1999; 10: 618.

79Nolan J. Fluid resuscitation for the trauma patient.

Resuscitation 2001; 48: 5769.

80Lang K, Boldt J, Suttner S, Haisch G. Colloids versus

crystalloids and tissue oxygen tension in patients

undergoing major abdominal surgery. Anesth Analg

2001; 93: 4059.

fluid choice for resuscitation of the trauma

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