• Users Online: 214
  • Print this page
  • Email this page

Year : 2009  |  Volume : 53  |  Issue : 5  |  Page : 592-607 Table of Contents     

Are All Colloids Same? How to Select the Right Colloid?

1 Associate Professor, Department of Anaesthesia & Intensive Care, Government Medical College & Hospital, Chandigarh, India
2 Junior Resident, Department of Anaesthesia & Intensive Care, Government Medical College & Hospital, Chandigarh, India

Date of Web Publication3-Mar-2010

Correspondence Address:
Sukanya Mitra
203-B, New Type-V Flats, Sector 24-A, Chandigarh 160023
Login to access the Email id

Source of Support: None, Conflict of Interest: None

PMID: 20640110

Rights and PermissionsRights and Permissions

The administration of intravenous fluids is one of the most common and universal interventions in medicine. Colloids are an alternative to the frequently used crystalloids, with highly variable use depending on a myriad of clinical variables. A colloid is defined as a high molecular weight (MW) substance that largely remains in the intravas­eular compartment, thereby generating an oncotic pressure. Colloids are considered to have a greater intravaseular persistence when compared to crystalloids. All colloids, however, are clearly not the same. Differences in the physi­cochemical properties, pharmacokinetics and safety profile exist amongst various colloids. This review explores the different types of colloids, with their properties and usefulness as well as adverse effects. While all the available colloids are reviewed briefly (e.g., albumin, gelatin, dextran) with respect to their pharmacology, indications, advan­tages and disadvantages, particular emphasis is laid on the hydroxyethyl starches (HES) because of their rising prominence. It is shown that HES differ widely in their physicochemical and pharmacokinetic properties, composition, usefulness, and especially in their adverse effect profiles. The third generation HES (tetrastarches), in particular, seem to offer a unique combination of safety and efficacy. Several issues related to this are discussed in detail. This review of the available clinical data demonstrates that HES should not be regarded as one homogenous group, and data for one product should not be automatically extrapolated to another. Thus, among the synthetic colloids, the tetrastarches appear to offer the best currently available compromise between efficacy, safety profile, and cost. They also appear to be the best suited for use in the intensive care setting. Finally, balanced (rather than saline-based) HES solutions appear promising as a plasma-adapted volume replacement strategy and may further refine the ongoing quest of finding the ideal fluid therapy.

Keywords: Colloids; Albumin; Dextran; Gelatin; Hydroxyethyl starch; Tetrastarch

How to cite this article:
Mitra S, Khandelwal P. Are All Colloids Same? How to Select the Right Colloid?. Indian J Anaesth 2009;53:592-607

How to cite this URL:
Mitra S, Khandelwal P. Are All Colloids Same? How to Select the Right Colloid?. Indian J Anaesth [serial online] 2009 [cited 2021 Mar 4];53:592-607. Available from: https://www.ijaweb.org/text.asp?2009/53/5/592/60338

   Introduction Top

The administration of intravenous fluids is one of the most common and universal interventions in medi­cine. Crystalloid solutions are the most frequently cho­sen, by far, with normal saline (NS) and lactated Ringer's (LR) both being the most frequent choices. Colloids are an alternative to ciystalloids, with highly variable use depending on a myriad of clinical variables.

Clinically available colloids have generally exhib­ited similar effectiveness in maintaining colloid oncotic pressure. Thus, colloids have been viewed as a class of essentially interchangeable fluids and selection of colloids has commonly been based on cost and conve­nience. But, are all colloids same? Differences in the physical properties, pharmacokinetics, pharmocodynamics and safety profile exist amongst various colloids - a review of these can help us to choose the right colloid in different clinical scenarios.

What is a colloid?

A colloid is defined as a high molecular weight (MW) substance that largelyremains inthe intravascu­lar compartment, thereby generating an oncotic pres­sure. Colloids are considered to have a greater intra­vascular persistence when compared to crystalloids. This property is lost, however, when capillary mem­branes are altered in a diseased state.

Colloids are of two types : [1],[2],[3],[4]

a. Natural, i, e., human albumin

b. Artificial, i.e., gelatin and dextran solutions, hydroxyethyl starches (HES).

How do various colloids differ in their properties?

Colloids have certain general characteristics which determine their behavior in the intravascular compart­ment. These, along with some other characteristics of the available colloids, are shown in [Table 1].

Molecular weight (MW): Two molecular weights are quoted for colloid solutions:

Mw : Weight average molecular weight

Mn : Number average molecular weight

The Mw determines the viscosity and Mn indi­cates the oncotic pressure. Albumin is saidto be mono­disperse because all molecules have the same molecu­lar weight (so Mw = Mn). Artificial colloids are all poly­disperse with molecules ofa range of molecular weights. [3]

Osmolality and oncotic pressure: Almost all colloid solutions have a normal ostmolality. The oncocity of the solution will influence the vascular expansion. The higher the oncotic pressure, the greater the initial vol­ume expansion . [3]

Plasma half-life: The plasma half-life of a colloid depends on its MW, the elimination route, and, the involved organ function (mainly eliminated by the renal route). Half-lives of colloids vary greatly.

Plasma volume expansion: The degree of volume expansion is mainly determined by the MW, whereas the intravascular persistence is determined by the elimination ofthe colloid. When compared to cry's­talloids, colloids induce a greaterplasmavolume ex­pansion forthe same administered volume. The dura­tion of volume expansion varies, however; unongthe different colloids. Gelatins have the shortest duration of volume expansion.

Acid-base composition: Albumin and gelatin solutions have physiological pH, while other solutions tend to have acidic pH.

Electrolyte content: The sodium concentra­tion is low in "salt-poor albumin". However, the so­dium content of other commercially available colloid solutions is similar to that of crystalloid solutions, while the potassium concentration differs. Urea-linked gela­tin solutions contain a small, but not negligible, concen­tration ofpotassium. Calcium, similarly, is also present in the gelatin solutions.

What are the various colloids available?

Human albumin solution

Albumin is the principal natural colloid compris­ing 50 to 60% of all plasma proteins. It contributes to 80% of the normal oncotic pressure in health. Albumin consists of a single polypeptide chain of 585 amino acids with a molecular weight of 69,000 Dalton. [1],[3],[5]


Albumin is synthesized only in the liver and has a half-life of approximately 20 days. After synthesis al­bumin is not stored but secreted into the blood stream with 42% remaining in the intravascular compartment [1] . When administered, two phases are observed. The first depends on the transcapillary exchange rate that cor­responds to the passage of albumin from the intravas­cularto the extravascular compartments which occurs with the help ofa transporter albondin. [3],[5],[6] The second phase is a function of the factional degradation rate.

Degree of volume expansion:

5°/a solution is isooncotic and leads to 80% ini­tial volume expansion whereas 25% solution is hyperoncotic and leads to 200 - 400% increase in volume within 30 minutes. The effect persists for 16­-24h. [2]


a. Emergency treatment of shock specially due to the loss of plasma [1]

b. Acute management of burns [1]

c. Fluid resuscitation in intensive care [5],[7]

d. Clinical situations of hypo-albumineamia

i. Following paracentesis [8]

ii Patients with liver cirrhosis (For extracorpo­real albumin dialysis (ECAD)) [8],[9],[10]

iii After liver transplantation [9]

e. Spontaneous bacterial peritonitis [10]

f. Acute lung injury [11]


1. Natural colloid: As albumin is a natural colloid it is associated with lesser side-effects like pruritus, ana­phylactoid reactions and coagulation abnormalities com­pared to synthetic colloids. [12]

2. Degree of volume expansion: 25%Albumin has a greater degree of volume expansion as compared to rest ofcolloids. 5% albumin solution has a similar degree of volume expansion as compared to hetastarch but greater than gelatins and dextrans.

3. Other benefits: Albumin acts a principal bind­ing protein of endogenous and exogenous substances. It also possesses antioxidant and scavenging effects. Albumin being negatively charged protein contributes to the formation of normal anion gap, influencing the acid-base status. [3],[13],[14]


1. Cost effectiveness: Albumin is expensive as compared to synthetic colloids.

2. Volume overload: In septic shock the release of inflammatory mediators has been implicated in in­creasingthe `leakiness' ofthe vascular endothelium. The administration of exogenous albumin may compound the problem by adding to the interstitial oedema. [15]


Dextrans are highly branched polysaccharide molecules which are available for use as an artificial colloid. They are produced by synthesis using the bac­terial enzyme dextran sucrase from the bacterium Leu­conostoc mesenteroides (B512 strain) which is growing in a sucrose medium. [16],[17]

Physicochemical properties:

Two dextran solutions are now most widely used, a 6% solution with an average molecular weight of 70,000 (dextran 70) and a 10% solution with an aver­age weight of 40,000 (dextran 40, low-molecular-weight dextran). [17]

Metabolism & Excretion

Kidneys primarily excrete dextrnn solutions. Smaller molecules (14000-18000 kDa) are excreted in 15 minutes, whereas larger molecules stay in circula­tion for several days. Up to 4O° /o of dextran-40 and 70% of dextran-70 remain in circulation at 12 h. [2],[16],[17]

Degree of volume expansion:

Both dextran-40 and dextran-70 lead to a higher volume expansion as compared to HES and 5% albu­men. The duration lasts for 6-12 hours. [2]


a. Dextran-40 is used mainly to improve micro­circulatory flow in microsurgical re-implantations.

b. Extracorporeal circulation: It has been used in extracorporeal circulation during cardio-pulmonary bypass.


1. Volume expansion: Dextrans leads to 100­150% increase in intravascularvolume. [2]

2. Microcirculation: Dextran 40 helps in improv­ing microcirculatory flow bytwo mechanisms, i.e., by decreasing the viscosity of blood by haemodilution and by inhibiting erythrocytic aggregation.


1. Anaphylactic reactions:
Dextrans cause more severe anaphylactic reactions than the gelatins or the starches. The reactions are due to dextran reactive antibodies which trigger the release of vasoactive me­diators. Incidence of reactions can be reduced bypre­treatment with a hapten (Dextran 1) [1],[12],[18]

2. Coagulation abnormalities: Dextrans lead to decreased platelet adhesiveness, decreased factor VIII, increased frbrinolysis and coating ofendothelium is decreased. Larger doses of dextran have been asso­ciated with significant bleeding complications. [1],[2],[4],[12]

3. Interference with cross-match: Dextrans coat the surface of red blood cells and can interfere with the abilityto cross-match blood. Dextrans also increase erythrocyte sedimentation rate. [19]

4. Precipitation of acute renal failure: Apos­sible mechanism for this is the accumulation of the dex­tran molecules in the renal tubules causing tubular plug­ging. Renal failure following dextran use is more of­ten reported when renal perfusion is reduced or when preexisting renal damage is present. [2],[3],[12],[20],[21]


Gelatin is the name given to the proteins formed when the connective tissues of animals are boiled. They have the property of dissolving in hot water and form­ing a jelly when cooled. Gelatin is thus a large molecu­lar weight protein formed from hydrolysis of col­lagen. [2],[3],[22] Gelatin solutions were first used as colloids in man in 1915. The early solutions had ahigh molecu­lar weight (about 100,000). This had the advantage of a significant oncotic effect butthe disadvantages of a high viscosity and atendencyto gel and solidify if stored at low temperatures. [22]

Several modified gelatin products are now avail­able; they have been collectively called the New-gen­eration Gelatins. There are 3 types of gelatin solutions currently in use in the world:

•Succinylated or modified fluid gelatins (e.g., Gelofusine, Plasmagel, Plasmion)

Urea-crosslinked gelatins (e.g., Polygeline)

Oxypolygelatins (e.g., Gelifundol)

Polygeline (`Haemaccel', Hoechst) is produced by the action of alkali and then boiling water (thermal degradation) on collagen from cattle bones. The re­sultant polypeptides (MW 12,000 - 15,000) are urea­crosslinked using hexamethyl di-isocyanate. The branching of the molecules lowers the gel melting point. The M W ranges from 5,000 to 50,000 with a weight­average MW of 35,000 and a number-average MW of 24,500. [3],[22]

Physiochemical properties:

Both Succinylated gelatin and polygeline are sup­plied as preservative-free, sterile solutions in sodium chloride. Polygeline is supplied as a 3.5% solution with electrolytes (Na + 145, K + 5. 1, Ca ++ 6.25& C1 - 145 mmol/l). As polygeline contains calcium ions it can be lead to increase in serum calcium concentration follow­ing large volume resuscitation. Polygeline also contains potassium ions: beneficial to those patients who are hypokalaemic. It is sterile, pyrogen free, contains no preservatives and has a recommended shelf-life of 3 years when stored at temperatures less than 30°C. Succinylated gelatin is supplied as 4% solution with electrolytes ((Na + 154, K + 0.4, Ca ++ 0.4 and Cl - 120 mmol/l). As it contains low chloride it is helpful for fluid resuscitation in patients with hyperchloremic acidosis. Also Succinylated gelatins are compatible with blood transfusions due to low calcium content. [22]


It is rapidly excreted by the kidney. Following in­fusion, its peak plasma concentration falls by half in 2.5 hours. Distribution (as a percent oftotal dose adminis­tered) by 24 hours is 71% in the urine, 16% extravas­cular and 13% in plasma. The amount metabolized is low: perhaps 3% [2],[3],[22]

Degree of volume expansion:

Gelatins lead to 70 to 80% of volume expansion. But duration of action is shorter in comparison to both albumin and starches. [3],[4],[22]


a. Hypovolemia due to acute blood loss.

b. Acute normovolaemic haemodilution. [23]

c. Extracorporeal circulation- cardiopulmonary by­ pass. [24]

d. Volume pre-loading prior to regional anaesthesia. [25]


1. Cost effective: It is cheaper as compared to albumin and other synthetic colloids.

2. No limit of infusion: Gelatins do not have any upper limit of volume that can be infused as compared to both starches and dextrans.

3. No effect of renal impairment: Gelatins are readily excreted by glomemlar filtration as they are small sized molecules. Gelatins are associated with lesser renal impairment as compared to HMW HES. [12],[22]


1. Anaphylactoid reactions: Gelatins are associ­ated with higher incidence of anaphylactoid reactions as compared to natural colloid albumin. [12]

2. Effect on coagulation: The effect of gelatins on coagulation is not clear. There are studies which sup­port activation of coagulation by gelatins [4] and there are some studies which reveal increased bleeding time, impaired platelet adhesiveness during cardiac surgery: [26]

3. Circulatorydisturbance: Gelatins are associated with occurrence of circulatory dysfunction marked by increased plasma renin activity and aldosterone in pa­tients with ascitis undergoing large-volume paracentesis. [27]

Hydroxyethyl starches (HES)

HES are derivatives of amylopectin, which is a highly branched compound of starch. Amylopectin structurally resembles glycogen. Amylopectin is rap­idly hydrolyzed with a 1/2 life of about 20 min. In order to make the amylopectin molecule more stable, anhydroxyethyl glucose residues are substituted with hydroxyethyl groups mainly at positions C 2 and C6 [2],[3],[28]

The first HES product, Hespan (DuPont Phar­maceuticals, Wilmington, DE), was made available in the United States inthe 1970s. Since then, further gen­erations ofHES have been developed, differing in their mean molecular weight (MW), molar substitution (MS), and C2/C6 ratio. Hydroxyethyl starches are identified bythree numbers, e.g., 10% HES 200/0.5 or 6% HES 130/0.4. The first number indicates the concentration of the solution, the second represents the mean MW expressed in kilo Dalton (kDa), and the third and most significant one is MS. These parameters are highly rel­evantto the pharmacokinetics of HES, as detailed be­low.

Physiochemical Properties:

HES preparations are characterized by the fol­lowing properties. [28],[29],[30]

1. Concentration: low (6%) or high (10%).

Concentration mainly influences the initial volume effect: 6%HES solutions are iso-oncotic in vivo, with 1 1 replacing about 1 1 of blood loss, whereas 10% solutions are hyperoncotic, with a volume effect con­siderably exceeding the infused volume (about 145%).

2. Average Molecular Weight (MW): low (=70 kDa), medium ( 200 kDa), or high (= 450 kDa).

In common with all ofthe synthetic colloids, HES are polydisperse systems containing particles with a wide range of molecular mass. In polydisperse systems, the determination of particle mass or relative molecular mass gives averages, which depend onthe method used as mentioned earlier (Mw and Mn). The ratio Mw/Mn gives an index of the degree of polydispersity in the system. When a polydisperse colloid is infused into the circulation, small molecules below the renal threshold (45 to 60 kDa7) are rapidly excreted, whereas the larger molecules are retained forvarying periods of time depending on their size and ease of breakdown. How­ever, osmotic effectiveness depends onthe number of particles, and not the molecular size; therefore, the ex­cretion of the smaller particles continuously reduces the osmotic effectiveness ofthe infused solution. This is compensated for bythe continuous supply of oncotically active molecules arising from degradation of larger frag­ments. Mean MW of the available products ranges from over 670 kDa to 70 kDa [Table 2].

3. Molar substitution (MS): low (0.45-0.58) or high (0.62-0.70)

The degree of substitution refers to the modifica­tion of the original substance by the addition of hydroxyethyl groups. The higher the degree of molar substitution, the greater the resistance to degradation, and consequently, the longer its intravascular persistence.

HES have a varying number ofhydroxyethyl resi­dues attached to the anhydrous glucose particles within the polymer. This substitution increases the solubility of the starch in water and, to a varying degree, inhibits the rate of destruction of the starch polymer by amylase. As with MW, there are two methods for calculating the degree of substitution on the starch polymer: The first of these is termed the degree ofsubstitution and is cal­culated from the number of substituted anhydroglucose residues divided by the total number of anhydroglucose residues. The second is generally referred to as the MS, which is calculated as the average number of hydroxyethyl groups reacted per anhydro glucose resi­due. The numbers represent the mass of the hydroxyethyl group and the anhydrous glucose resi­due, respectively.

M S is thus the average number ofhydroxyethyl residues ner glucose subunit. The figure 0.7 in the de­scription of a HES preparation indicates that there are seven hydroxyethyl residues on average per 10 glu­cose subunits. Starches with this level of substitution are called hetastarches, and similar names are applied to describe other levels of substitution: hexastarch (MS 0.6), pentastarch (MS 0.5), and tetrastarch (MS 0.4).

Unsubstituted anhydroglucose units are more prone to enzymatic degradation by alpha amylase; therefore, hydroxyethylation slows down the rate of enzymatic breakdown of the HES molecule and prolongs intra­vascular retention time. Thus, older generation HES products with high MS accumulate in the plasma, un­like the latest generation of tetrastarches.

4. C2/C6 ratio: low (<8) or high (>8).

The C2/C6 ratio refers to the site where substitu­tion has occurred on the initial glucose molecule. The higher the C2/C6 ratio, longer the half-life and hence, longer persistence in the blood. Thus, the pattern of hydroxyethylation also has a significant impact on the pharmacokinetic properties, but this may not be ap­preciated because it does not appear in the usual prod­uct specification alongside MW and MS. Hydroxyethylation of the glucose subunits is guided predominantly towards the C2 and C6 carbon atoms. Hydroxyethyl groups at the position of the C2 atom urhibitthe access of alpha-amylaseto the substrate more effectivelythan do hydroxyethyl groups at the C6 po­sition. Hence, HES products with high C2/C6 ratios are expected to be more slowly degraded.

11 . Metabolism:

Following the infusion of HES there is initially a rapid amylase-dependent breakdown and renal excre­tion. Plasma half life is 5 days and 90% is eliminated in 42 days. [30] Smaller HES molecules (<50,000 to 60,000 Dalton) are eliminated rapidly by glomerular filtration. Medium sized molecules get excreted into the bile and faeces. Another fraction is taken up bythe reticuloen­dothelial system (RES) where the starch is slowly bro­ken down. Thus, trace amounts ofthe preparations can be detected for several weeks after administration. [1],[2],[3]

Degree of volume expansion:

The increase in colloid osmotic pressure obtained with HES is equivalentto albumin. HES results in 100% volume expansion similar to 5% albumin. It results in greater volume expansion as compared to gelatins. [31] Duration ofvolume expansion is usually 8-12 h. [2]


a) Stabilization of systemic haemodynamics.

b) Anti-inflammatory properties: HES has been shown to preserve intestinal microvascular perfusion in endotoxaemia due to their anti-inflammatory properties. [32]


1. Cost effectiveness: HES is less expensive as comparedto albumin and is associated with a compa­rable volume of expansion.

2. Maximum allowable volume: Maximum vol­ume which can be transfused ofmedium weight HE S (130 kDa) with medium degree of substitution (0.4) is 50 ml/kg. This is greater as compared to other syn­thetic colloids like dextrans.


The first and second-generation HES (Hextend, Hetastarch, Pentastarch) are associated with various side-effects as follows:

1. Coagulation: HES administration is associated with reduction in circulating factor VIII and von Willebrand factor levels, impairment of platelet func­tion, prolongation of partial thromboplastin time and activated partial thromboplastin time and increases bleeding complications. [2],[4],[12],[29]

2. Accumulation: High molecular weight (HMW) HES are associated with greater degree of accumula­tion in interstitial spaces and reticulo-endothelial sys­tem. It gets deposited in various tissues including skin, liver, muscle, spleen, intestine, trophoblast and placen­tal stroma. Such depositions have been associated with pruritus. [2],[12],[33]

3. Anaphylactoid Reactions: HES is associated with higher incidence of anaphylactoid reactions as compared to other synthetic colloids as well as albu­min. [12]

4. Renal impairment: HMW HES has been found to be associated with increased creatinine levels, oliguria, acute renal failure in patients who were criti­cally ill with existing renal impairment. [34],[35] HMW HES is associated with development of osmotic nephrosis like lesions in both proximal and distal renal tubules. [35] Cittanova et al demonstrated that the use of 6% HES 200/0.62 (2,100 ± 660 ml) in brain-dead donors re­sulted in impaired renal function in kidney transplant recipients. [36] Thus, HES preparations with high molecu­lar weight and/or high MS may have detrimental con­sequences for renal function. Modern HES prepara­tions with lower Mw, lower MS (e.g., HES 130/0.4) have been shown to have no more negative influence on kidney function.

5. Increase in amylase levels: HES infusion is an occasional elevation of the serum amylase levels. But this has no clinical implication as such. [23]

However, it is important to consider the data for individual products and not to extrapolate reports from one HES type to another. Clinical studies have revealed significant differences between the HES generations regarding coagulation, tissue storage, and renal function. The next section on "third-generation" HES (also known as tetrastarch) clearly brings outthis important point.

Third-generation HES: tetrastarch

The development of newer starch-based plasma volume expanders has been driven by a need to im­prove safety and pharmacological properties while maintainingthe volume efficacy of previous HES gen­erations. [28],[37] Reductions in MW and MS have led to products with shorter half-lives, improved pharmaco­kinetic and pharmacodynamic properties, and fewer side effects. Although earlier products were derived from amylopectin extracted from waxy maize starch, it is inaccurate to refer to HES as if they were only one homogenous product because modifications to MW and the degree and pattern of substitution result in dis­tinct and observable differences between and within the different generations of HES. The same is true for starches of similar structure that have been derived from different source materials: waxy maize and potato. Two third-generation starches based onthese two materials are currently available un various formulations. According to one study, potato and waxy maize-derived HES solutions are not bioequivalent. [38] Therefore, findings obtained from studies using one type may not be valid for the other.

Safety profile oftetrastarches vis-a-vis earlier-genera­tion HES

Effects on Coagulation and Platelet Fiuiction: A number of studies have investigated the in vitro and in vivo effects of various HES products on coagulation and platelet function. Overall, the more rapidly degrad­able HES products have been found to have a greatly reduced effect on the coagulation process compared to older products. The most useful evidence concern­ing the safety of waxy maize-derived 6% HES 130/0.4 is derived from extensive clinical studies in many types of maj or surgery. Although very high doses have been used, no adverse effects on coagulation have been re­ported compared to controls using lower doses.

A pooled analysis of prospective and random­ized studies comparing 6% HES 130/0.4 with 6% HES 200i0.5 in patients undergoing major surgical proce­dures (n = 449) was carried out by Kozek­Langenecker et a1. [39] The authors concluded that HES 130/0.4 was associated with a significant reduction in perioperative blood loss, both estimated and calculated, and that there was a significant reduction in transfusion needs. The reduction inthe volume of erythrocyte loss and in transfusion needs was in the order of one red blood cell unit for both parameters.

A meta-analysis including 73 randomized trials compared the clinical outcome in adult patients receiv­ing colloids in the perioperative period. [40] HES were stratified according to MS. It was found that tetrastarches were associated with a 15% reduction in blood loss compared to gelatin and pentastarches. Pentastarches were associated with larger peri operative blood loss (10%) as compared to albumin. All other clinical outcome variables were similar between groups. The evidence base for waxy maize-derived HES (6% 130/0.4) is particularly strong; overall, there are more than 50 published studies reporting on the coagulation effects ofwaxy maize-derived HES 130/0.4, including more than 20 Phase II to IV studies. These studies confirm that, unlike earlier generation HES prepara­tions, the tetrastarches have minimal effect on coagula­tion. [28]

Accumulation and Tissue Storage: HES mol­ecules with a higher in vivo MW resulting from increased MS tend to be stored in tissue before being metabo­lized by amylases. Due to the more rapid clearance of the latest generation oftetrastarches, it is expected that tissue accumulation and its clinical manifestations will not be observed with the same frequency as compared to older starches. The main clinical manifestation of tis­sue storage is HES-related pruritus, which was first reported in otologic patients who had received rela­tively high repeated doses ofHES. The pruritus arises from long-term cutaneous storage of HES molecules, and it may last for months after exposure. The inci­dence appears to be related to the MS and the cumulative infused dose, and it is resistant to treatment by glucocorticoids, antihistamines, acetaminophen, and neuroleptic drugs. By comparison, Ellger et al found no incidence ofpostoperative itching in any of the 40 patients undergoing elective urologic cancer surgery, although relatively high doses of waxy maize-derived HES 130/0.4 (6%) were given.¢' In other studies of HES 130/0.4 using relatively high doses, pruritus did not seem to be a clinical problem. [42],[43]

Effects on Plasma Bilirubin: Waxy maize-de­rived HES 130/0.4 has been extensively studied in a large number of clinical trials. None of these reports suggests that it is associated with deterioration of liver function compared to controls. However, potato-de­rived HES 130/0.42 is the onlytetrastarch to be abso­lutely contraindicated in patients with severe hepatic impairment. [28]

Effects on Renal Function: Anumber of earlier reports suggest that HES products may have adverse effects on renal function. [34],[35],[36] However, more recent studies using third-generation products have not re­ported unfavorable effects, suggesting that the lower tendency of these products to accumulate may improve their profile with regard to renal function.

An important large-scale observational study of the effects of HES administration on renal function was carried out by Sakr et al. [44] In a retrospective analysis of data of 3147 critically ill patients included in the SOAP study (Sepsis Occurrence in Acutely Ill Patients), it was found that HES per se was not an independent risk factor for adverse effects on renal function in the 1,075 patients who received HES. Neither the use of HES nor the dose administered was associated with an increased risk ofrenal replacementtherapy, even in the subgroup of patients with severe sepsis and septic shock (n= 822). These patients were also at particular risk for renal dysfunction because of a high incidence of cardiovascular dysfunction and preexisting renal im­pairment. Unfortunately, the authors did not distinguish between the types of HES preparations used; how­ever, they did acknowledge that the use of newer HES preparations with a lowertendencyto accumulate may have contributed to the favorable results.

In the considerable body of clinical data on the third generation HES 130/0.4, there have been no re­ports of adverse effects on renal function over and above those seen in control groups inpatients who are considered to be at particular risk, such as those with previous mild to severe renal dysfunction, [45] the eld­erly, [46] and those receiving high-dose therapy. [47]

In summary, the published data onthis topic sug­gest that there are differences between the older and newer generations of HES and that the reports of ad­verse effects on renal function should not be extrapo­lated to newer HES products. Nine clinical trials on renal function demonstrate the safety of waxy maize­derived HES 130/0.4, and two recently published tri­als confirm that potato-derived HES 130/0.42 has no adverse effects on renal function either. [28],[37]

Special Patient Groups: Extra caution is always needed when treating high-risk groups, such as the eld­erly, children, and those with renal impairment Due to a higher incidence of comorbidities and changes in lung, kidney and cardiovascular function, the elderly are at increased risk for impairment of renal function. The waxy maize-derived tetrastarch HES 130/0.4 has been thor­oughly studied in these groups and has a well-docu­mented safety profile. In the elderly, HES 130/0.4 has been studied in patients undergoing abdominal surgery, where it was found to be an adequate replacement for albumin or gelatin. In cardiac surgery patients, HES 130/0.4 was deemedto be as safe as gelatin, offering a more persistent volume effect and a lower risk of ana­phylactoid reaction. Further studies on HES 130/0.4 have also confirmed its safety in surgery, where pa­tients are athighriskforrenal dysfunction: abdominal aortic surgery, spinal fusion surgery, and surgery for aortic aneurysm. [28],[37],[45]

Waxy maize-derived HES 130/0.4 is the only third generation HES with controlled clinical data in chil­dren. In this context, Standl et al reported that waxy maize-derived 6% HES 130/0.4 was as safe and well tolerated as albumin when used in pediatric surgery. [48] Other studies reached similar conclusions when using 6% HES 130/0.4 and 4% albumin in pediatric cardiac surgery and spinal fusion, whereas Sumpelmann et al reported a very low level of adverse reactions with potato-derived HES 130/0.42 in a noncomparative observational study in children. [49]

Effects on Microcirculation and Oxygen­ation: There is increasing evidence that some plasma substitutes possess additional properties that have ben­eficial effects on organ perfusion, microcirculation, tis­sue oxygenation, inflammation, endothelial activation, capillary leakage, and tissue edema over and above theirvolume replacement effects. Hypovolaemiamay initiate a cascade of pathophysiological processes, such as stimulation of the sympathoadrenergic and renin­angiotensin systems that may result in inadequate tissue perfusion and decreased oxygen supply to the tissues. Ideally; therefore, fluid therapy should confer benefi­cial effects on microcirculation and tissue oxygenation.

Third generation HES 130/0.4 has positive ef­fects on tissue oxygenation and microcirculation in pa­tients undergoing major abdominal surgery [50] Intravas­cular volume replacement with a 6% solution improved tissue oxygenation compared with a crystalloid-based volume replacement strategy using lactated Ringer's ti­trated to similar hemodynamic endpoints. The tetrastarch was also found to produce a greater and earlier increase oftissue oxygen tension as compared to two pentastarch solutions (6% HES 70/0.5 and 6% HES 200/0.5) when administered to volunteers and a more pronounced and earlier increase of skeletal muscle oxygen tension. Lang et a1 [50] attribute these beneficial effects oftetrastarches to improved microperfusion and reduced endothelial swelling; crystalloids mostly dis­tribute in the interstitium, causing endothelial tissue swell­ing and reduced capillary perfusion. Neff et a1 [51] sug­gest that HES with lower MS may decrease erythro­cyte aggregation, thereby reducing low-shear viscos ity of the blood. However, more studies are needed to investigate this issue more thoroughly. [28]

Colloid vs. crystalloid for volume resuscita­tion in the critically ill

So, are both colloids and crystalloids safe and effective means of intravenous fluid resuscitation? Al­though this has been the most common assumption over the past 60 years, it may not be true. The safety of colloids was fast questioned by a rudimentary meta­analys is performed by Velanovich [52] in 1989. Since that time, there have been a number of other more elegant systematic reviews thathave similarly questionedthe safety of colloids. The first of these were published in BMJ in 1998 in which one systematic review ques­tioned the safety of colloids in general [53] and another questioned specifically the safety of albumin. [7] Both of these meta-analyses suggested that there was a small but statistically significant increase in the risk of death for patients who received colloids over crystalloids. Since that time, there has been a rigorous and more focused meta analysis, including an assessment ofpo­tential morbid complications of colloid use, which found no difference in outcome among patients treated with colloids or crystalloids. [54]

However, the questions regarding the safety of col­loids remained in clinicians' minds and circulated in the literature. Based on these concerns, the Australia and New Zealand Intensive Care Society's Clinical Trials Group (ANZICS-CTG) designed and conducted one of the largest critical care trials in history. [55] The SAFE (alive versus Albumin Fluid Evaluation) trial random­ized 7000 critically ill patients requiring fluid resuscita­tion to receive isooncotic albumin or isotonic crystalloid. In this study, there was no overall difference in outcome according to whether patients received colloids or crys­talloids (relative risk for death with colloid use = 0.99, 95% confidence interval 0.91-1.09,P = 0.87).

Clinical efficacy of different colloids

Important effects of prophylactic or therapeutic administration of HES colloids are the maintenance and rapid restoration of intravascular volume. Besides these effects on macrocr culation, effects on microcirculation and tissue oxygenation are importantforthe preserva­tion of organ function. HES 130/0.4(6%) was found superior regarding tissue oxygenation when compared with crystalloids in major abdominal surgery, [50] and pro­vided a larger and faster increase of tissue oxygen ten­sion when compared with other HES solutions after infusion in volunteers. [56]

HES differs from other pharmaceutical active in­gredients like small molecules or albumin because of its polydispersity and because of changes in molecular weight from in vitro to in vivo situations. Pharmacoki­netic parameters such as half-lives cannot be defined rigorously. HES clearances and residual HES concen­trations after 24 hours, however; clearly depend on the molar substitution and the C2/C6 ratio, whereas the initial mean molecular weight in the bottle is of second­ary importance. In the case of HES products, plasma concentration half-lives should not erroneously be in­terpreted as efficacy half-lives. Intravascular volume is known to be regulated by a number of mechanisms including the colloid osmotic pressure which is raised by infusion of colloid solutions. Counter-regulatory mechanisms afterplasmavolume expansion haveto be taken into account. Therefore, the extent and duration of the volume effects induced bythe infusion solution, besides the type of infusion, also highly depend on the individual patient's condition, blood loss status, infu­sion dose and speed. A longer plasma persistence of HES was initially regarded as favorable as this was thought to result in a prolonged volume effect. A large number of studies, including initial uncontrolled obser­vations till recent double-blind randomized controlled trials clearly demonstrate that this beliefwas not justi­fied. [57],[58],[59] For example, a recent double-blind study by Gandhi et a1 [60] performed in the USA investigated the efficacy and safety of HES 130/0.4 and HES 670/0.75 in patients undergoing major orthopaedic surgery. In­fusion of the colloids was guided by a predefined algo­rithm taking central venous pressure and arterial blood pressure into account. The results clearly showed that both colloids were equally effective in the stabilization of haemodynamics. Volume of infused crystalloids was similar in both groups.

Current guidelines on initial haemodynamic stabi­lization in shock states suggest infusion of either natural or artificial colloids or crystalloids. However; as the volume of distribution is much larger for crystalloids than for colloids, resuscitation with crystalloids alone requires more fluid and results in more oedema, and may thus be inferior to combination therapy with col­loids. According to a latest critical review ofthe use of various colloids in intensive care medicine, [61] dextrans appear to have the most unfavourable riskbeneft ratio among the currently available synthetic colloids due to their relevant anaphylactoid potential, risk of renal fail­ure and, particularly; their major impact on haemostasis. The effects of gelatin on kidney function are currently unclear; but potential disadvantages of gelatin include a high anaphylactoid potential and a limited volume ef­fect compared with dextrans and HESS. Modern HES preparations have the lowest risk of anaphylactic reac­tions amongthe synthetic colloids. Older HES prepa­rations (hetastarch, hexastarch and pentastarch) have repeatedly been reported to impair renal function and haemostasis, especially when the dose limit provided by the manufacturer is exceeded, but no such effects have been reported to date for modern tetrastarches compared with gelatin and albumin. However; no large­scale clinical studies have investigated the impact of tetrastarches on the incidence of renal failure in criti­cally ill patients. When considering the efficacy and risk/ benefit profile of synthetic colloids, modem tetrastarches appear to be most suitable for intensive care medicine, given their high volume effect, low anaphylactic poten­tial and predictable pharmacokinetics. However, the impact of tetrastarch solutions on mortality and renal function in septic patients has not been fully determined, and further comparison with crystalloids in prospec­tive, randomized studies is required. [61]

Saline versus balanced HES

Conventional HES solutions consist of saline with abnormally high concentrations of sodium (154 mmoU 1) and chloride (154 mmolll). Atotal balanced volume replacement strategy is a new concept for correcting hypovolemia. To fulfill this concept, balanced colloids, for example, balanced hydroxyethyl starch (HES) so­lutions, are necessary in addition to balanced crystal­bids. In animal as well as in human studies, the use of HES dissolved in a plasma-adapted solution showed beneficial effects on acid-base status compared with conventional HES dissolved in saline (reviewed recently by Boldt [62] ). As the base excess is an important surro­gate marker for identifying patients with malperfused tissues, infusion of considerable amounts of unbalanced HES solutions producing low base excess would pos­sibly result in inappropriate clinical interventions. Bal­ancing the HES preparation was associated with sig­nificantly fewer alterations in coagulation; dilution of blood with balanced HES showed significantly fewer negative effects on thrombelastography and platelet aggregation than conventional HES. Whether modula­tion of the acid-base status by a balanced volume re­placement strategy would beneficially influence organ function, morbidity or even mortality in the critically ill must be evaluated in large controlled future studies. At present, arguing against a total balanced volume re­placement strategy appears to be difficult. Balanced HES solutions complete the idea of a plasma-adapted volume replacement strategy and may add another piece to the puzzle of finding the ideal fluid therapy for treat­ingthe hypovolemic patient. [62]

Making a choice in regards to colloids requires the clinician to have athorough knowledge of the dif­ferent properties and side-effects of various available preparations. Laboratory, animal, and clinical studies all demonstrate that there are clear physicochemical and pharmacokinetic differences between the generations of HES, mainly resulting from modifications to the MS and the pattern of substitution. Both of these result in differences in the in vivo MW as well as plasma and tissue persistence. Apparently small variations in MS have significant effects on the coagulation system and renal function. Notably, the third generation of tetrastarches shows a significantly improved safety pro­file without any loss of volume effect compared to first­and second generation HES preparations. The increased safety margin of HES 130/0.4 was recognized by Eu­ropean regulatory authorities when the maximum daily dose was increased to 50 mL/kg which is the highest dose limit for any HES type approved for human use so far: Variation in the source material for HES also produces measurable pharmacokinetic differences in the end product. This review ofthe available clinical data demonstrates that HES should not be regarded as one homogenous group, and data for one product should not be extrapolated to another.

The development of new HES molecules was guided towards faster and more complete elimination. Forthe latest generation HES (molar substitution 0.4), clearances more than 23 times higher than for first-gen­eration hetastarch and almost five times higher than for second generation pentastarch have been shown. Con­sequently, tissue storage could be greatlyreduced, and plasma accumulation is virtually absent after multiple dosing. Nevertheless, as proven by several well-de­signed double-blind trials, volume efficacy of HES 130/ 0.4 is equivalent to HES 200/0.5 as well as to HES 670/0.75. The prior belief that prolonged intravascular retention is associated with aprolonged volume effect was not justified, as even slowly metabolizable HES types do not cause considerable volume effects 24 hours after the last administration.

Complex issues exist when discussing intravenous fluids. Amore logical approach is to selectthe type of fluid that is best designed to treat a specific problem. Crystalloid fluids should be used in patients with dehy­dration, i.e., with loss of both interstitial and intravas­cular fluid. Colloid fluids are designed to stay in the intravascular space. Currently available evidence sug­gests that perioperative volume therapy should aim at optimizing plasma volume against dynamic endpoints using colloid. Crystalloid use should be limited to re­placement of deficits and ongoing clear-fluid losses. Among the synthetic colloids, the tetrastarches appear to offer the best currently available compromise be­tween the cost of products such as albumin and safety profile. Finally, balanced HES solutions appear prom­ising as a plasma-adapted volume replacement strat­egy and may further refine our ongoing quest of finding the ideal fluid therapy.

   References Top

1.Kaye AD, Kucera IJ. Intmvascular fluid and electrolyte physiology. In, Miller RD, ed. Miller's Anesthesia, 6 th edi­tion. Philadelphia, Churchill Livingstone: 2005,1763-98.  Back to cited text no. 1      
2.Martin P ed. Colloid and crystalloid resuscitation. The ICU Book, 3rd edition. Philadelphia, Churchill Livingstone: 2007,233-54.  Back to cited text no. 2      
3.Dubois MJ, Vincent IL. Colloid Fluids. In, Hahn RG, Prough DS, Svensen CH, eds. Perioperative Fluid Therapy, 1't edition. New York, Wiley: 2007, 153-611.  Back to cited text no. 3      
4.Linder P, Ickx B. The effects of colloid solutions on he­mostasis. Can JAnesth 2006; 53: s30-39.  Back to cited text no. 4      
5.Nicholson J, Wolmaris M, Park G The role of albumin in critical illness. Br JAnaesth 2000; 85: 599-610.  Back to cited text no. 5      
6.Schnitzer JE, Carley WW P41ade GE. Specific albumin binding to microvascular endothelium in culture. Am J Physiol 1988; 254:H425-27.  Back to cited text no. 6      
7.Cochrane Injuries Group Albumin Reviewers: Human Album in administration in critically ill patients: System­atic review of random ized controlled trials. BMJ 1998; 317: 235-240.  Back to cited text no. 7      
8.Sort P, Navasa M, Arroyo V et al. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl JMed 1999; 341:403-409.  Back to cited text no. 8      
9.Joseph S and Park G Properties and use of albumin. Intravenous Fluid Therapy, Chapter 5, Therapeutics: (eds) WebbAR, 2003: B. BrawnMedical Ltd., Germany.  Back to cited text no. 9      
10.Gines P, CardenasA, Arroyo V, Rodes J. Management of cirrhosis and ascites. N Engl J Med 2004;350: 1646-1654.  Back to cited text no. 10      
11.Martin GS, Mangialardi RJ, Wheeler AP, Dupont WD, Morris JA, Bernard GR. Albumin and furosemide therapy in hypoproteinemic patients with acute lung injury. Crit CareMed 2002; 30:2175-2182.  Back to cited text no. 11      
12.Barron ME, Wilkes, Navickis RJ. Asystematic review of the comparative safety of colloids. Arch Surg 2004;139: 552-563.  Back to cited text no. 12      
13.DriscollDF, McMohanM, Blackburn GL, BristrianBR. Phenytoin toxicity in a critically ill,hypoalbuminemic patientwith normal serum drug concentrations. Crit Care Med 1988;16:1248-49.  Back to cited text no. 13      
14.Mimoz O, Soreda S, Padoin C, Tod M, Petitjean O, Benham ouD. Ceftriaxone pharmacokinetics during ia­trogenic hydroxyethyl starch-induced hypoalbumin­emia: a model to explore the effects of decreased protein binding capacity on highly bound drugs. Anesthesiol­oav 2000:93:735-43.  Back to cited text no. 14      
15.Park G. Molecular mechanisms of drug metabolism in the critically ill. Br JAnaesth 1996; 77:32-49.  Back to cited text no. 15      
16.Arthurson G, Granath K, Thoren L, Wallenius G. The renal excretion of LMW dextran.Acta Clin Scand 1964; 127: 543-51.  Back to cited text no. 16      
17.Atik M. Dextran-40 and dextran-70, a review. Arch Surg 1967; 94:664-67.  Back to cited text no. 17      
18.Fordhoff A. Anaphylactoid reactions to dextran -Are­port of 133 cases. Acta Anaesthesiol Scand 1977; 21: 161-67.  Back to cited text no. 18      
19.NearmanHS, Herman ML. Toxic effects of colloids in the intensive care unit. Crit Care Clin 1991; 7:713-23.  Back to cited text no. 19      
20.Mailoux L, Swartz CD, Capizzi R, et al. Acute renal fail­ure after administration of LMW dextran. N Engl J Med 1967;277: 1113-18.  Back to cited text no. 20      
21.Drumi W, Polzleitner D, LaggnerAN et al. Dextran-40, acute renal failure and elevated plasma oncotic pres­sure. NEngl JMed 1988;318: 252-54.  Back to cited text no. 21      
22.Roberts J, Nightingale P. Properties and use of gelatins. In, WebbAR, ed. Therapeutics. Germany, Braun: 2003, 45-52.  Back to cited text no. 22      
23.Goodnough L, Monk T. Autologous transfusion: in Miller'sAnesthesia. ed Miller RD, 6d' edition. Philadel­phia, 2005:1831-1843.  Back to cited text no. 23      
24.Nyhan D, Johns RA. Anesthesia for cardiac surgery procedures: in Miller's Anesthesia, ed Miller RD, 6th edition, Philadelphia, 2005,1941-2004.  Back to cited text no. 24      
25.Baraka AS, Taha SK, Ghabach MB, Sibaii AA, Nader AM. Intravascular administration of polymerized gela­tin versus isotonic saline for prevention of spinal-in­duced hypotension. AnesthAnalg 1994; 78: 301-5.  Back to cited text no. 25      
26.Tabuchi N, Haan J, Gallandat RC, Boonstra PW, vanOeveren W Gelatin use impairs platelet adhesion dur­ing cardiac surgery. Thromb Haemost 1995; 74: 1447-51.  Back to cited text no. 26      
27.Gines A, Fernandez-Esparrach G, Monescillo A, et al. Randomized trial comparing albumin, dextran-70 and polygehne in cirrhotic patients with ascitis treated by paracentesis. Gasteroenterology. 1996;111: 1002-10.  Back to cited text no. 27      
28.Westphal M, James MFM, Kozek-Langenecker SA, StockerR, GuidetB, Van Aken H. Hydroxyethyl starches. Different products - different effects. Anesthesiology 2009;111:187-202.  Back to cited text no. 28      
29.Treib J, HaassA, Pindur G Coagulation disorders caused by hydroxyethyl starch. Thromb Haemost 1997; 78: 974-83.  Back to cited text no. 29      
30.Yacobu A, Stoll RG, Sum CY. Pharmacokinetics of hydroxyethyl starch in normal subjects. J Clin Pharmacol 1982; 22: 206-12.  Back to cited text no. 30      
31.Solanke TF, Khwaja MS, Kadomemu EL. Plasma volume studies with four different plasma volume expanders. J Surg Res 1971;11:140-43  Back to cited text no. 31      
32.Schaper J et al. Volume therapy with colloid solutions preserves intestinal microvascular perfusion in endotoxaemia. Eur JHeart Failure 2008; 76:120-128.  Back to cited text no. 32      
33.Sirti C, Laubenthal H, Zumtobel V; Kraft D, Jurecka W. Tissue deposits of hydroxyethyl starch (HES): dose- de­pendent and tune- related. Br JAnaesth 1999; 82:510-513.  Back to cited text no. 33      
34.Schortgen F et al. Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: a multicentre randomized study. Lancet 2001 ;357:91 1-16.  Back to cited text no. 34      
35.Davidson IS. Renal impact of fluid management with colloids: a comparative review. Eur JAnaesthesiol 2006; 23:721-738.  Back to cited text no. 35      
36.Cittanova lviL, Leblanc I, Legendre CH, et al. Effect of hydroxyethylstarch in brain-dead kidney donors on re­nal function in kidney-transplant recipients. Lancet 1996:348; 1620-1622  Back to cited text no. 36      
37.James MFM. The role of tetrastarches for volume re­placement in the perioperative setting. Curr Opin Anaesthesiol 2008; 21: 674-678.  Back to cited text no. 37      
38.LehmannG, Marx G, Forster H. Bioequivalence compari­son between hydroxyethyl starch 130/0.42/6:1 and hydroxyethyl starch 130/0.4/9:1. DrugsRD 2007; 8: 229­240.  Back to cited text no. 38      
39.Kozek-Langenecker SA, Jungheinrich C, Sauennann W van der Linden PS. The effects of hydroxyethyl starch 130/0.4(6%) onblood loss and use of blood products in major surgery: Apooled analysis of random ized clinical trials. AnesthAnalg 2008;107:382-390.  Back to cited text no. 39      
40.Cheng D, Behsle S, Giffin M, Karkouti K, Martin J, James M, et al. Colloids for perioperative plasma volume ex­pansion: Systematic review with meta-analysis of con­trolled trials (Abstract). Transfus Altem Transfus Med 2007;9:S3.  Back to cited text no. 40      
41.Ellger B, Freyhoff J, Van Aken H, Booke M, Markus MA. High dose volume replacement using HES 130/0.4 during major surgery. Impact on coagulation and inci­dence of postoperative itching. Neth Tijdschr Anesth 2006;19:63-68.  Back to cited text no. 41      
42.Klemm E, Bepperling F, Burschka MA, Mosges R. He­m odilution therapy with hydroxyethyl starch solution (130/0.4) in unilateral idiopathic sudden sensorineural hearing loss: A dose-finding, double-blind, placebo­controlled, international multicenter trial with 210 pa­tients. OtolNeurotol2007; 28:157-170.  Back to cited text no. 42      
43.Van der Linden PS, de HertSG DeraedtD, Cromheecke S, de Decker K, de Paep R, et al. Hydroxyethyl starch 130/0.4 versus modified fluid gelatin forvolume expan­sion in cardiac surgery patients: The effects on perioperative bleeding and transfusion needs. Anesth Analg 2005;101:629-634.  Back to cited text no. 43      
44.SakrY;PayenD,ReinhartK,SipmannF,ZavalaB,Bewley J, et al. Effects of hydroxyethyl starch administration on renal function in critically ill patients. Br JAnaesth 2007; 98:216-224.  Back to cited text no. 44      
45.Boldt J, Brosch C, Ducke M, Papsdorf M, LehmannA. Influence of volume therapy with a modern hydroxyethylstarch preparation on kidney function in cardiac surgery patients with compromised renal func­tion: A comparison with human album in. Crit Care Med 2007; 35:2740-2746.  Back to cited text no. 45      
46.Fenger-Eriksen C, Hartig RC, Kappel JT, Anker-Moller E, Heslop J, Frokiaer J, Tr nnesen E. Renal effects of hypotensive anaesthesia in combination with acute nonnovolaem is haemodilution with hydroxyethyl starch 130/0.4 or isotonic saline. ActaAnaesthesiol Scand 2005; 49:969-974.  Back to cited text no. 46      
47.Neff TA, Doe lberg M, Jungheinrich C, SauerlandA, Spahn DR, Stocker R. Repetitive large-dose infusion of the novel hydroxyethyl starch 130/0.4 in patients with severe head injury. AnesthAnalg 2003; 96:1453­1459.  Back to cited text no. 47      
48.Stand/ T, Lochbuehler H, Galli C, ReichA, Dietrich G, Hagemann H. HES 130/0.4 (Voluven®) or human al­bumin in children younger than 2 yr undergoing non­cardiac surgery. Aprospective, randomized, open la­bel, multicentre trial. Eur JAnaesthesiol 2008; 25:437­445.  Back to cited text no. 48      
49.Sumpelmann R, Kretz FJ, Gabler R, Luntzer R, Baroncini S, Osterkorn D, et al. Hydroxyethyl starch 130/0.42/6:1 for perioperative plasma volume replace­ment in children: Preliminary results of a European Prospective Multicenter Observational Postauthorization Safety Study (PASS). Paediatr Anaesth 2008; 18:929-933.  Back to cited text no. 49      
50.Lang K, Boldt J, Suttner S, Haisch G. Colloids versus crystalloids and tissue oxygen tension in patients un­dergoing major abdominal surgery. AnesthAnalg 2001; 93:40_51109.  Back to cited text no. 50      
51.Neff TA, Fischler L, Mark Ivi, Stocker R, Reinhart WH. The influence of two different hydroxyethyl starch so­lutions (6% HES 130/0.4 and 200/0.5) on blood viscos­ity. AnesthAnalg 2005;100:1773-1780.  Back to cited text no. 51      
52.Velanovich V Crystalloid versus colloid fluid resus­citation: a metaanalysis of mortality. Surgery 1989; 105:65-71.  Back to cited text no. 52      
53.Schierhout G, Roberts I. Fluid resuscitation with colloid or crystalloid solutions in critically ill patients: a system­atic review of randomized trials. BMJ 1998; 316:961-64.  Back to cited text no. 53      
54.Choi PT, Yip G, Quinonez LG, CookDJ. Crystalloids vs. colloids in fluid resuscitation: a systematic review. Crit Care Med 1999; 27:200-210.  Back to cited text no. 54      
55.Finfer S, Bellomo R, Boyce N, French J, Myburgh J, Norton R; SAFE Study Investigators. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med 2004; 350: 2247­2256.  Back to cited text no. 55      
56.StandlT, BurmeisterMA, SchroederF, CurrlinE, Schulte am Esch J, et al. Hydroxyethyl starch (130/0.4) provides larger and faster increases in tissue oxygen tension in comparison with prehemodilution values than HES 70/ 0.5 or HE S 200/0.5 in volunteers undergoing acute normovolemic hemodilution. Anesth Analg 2003; 96:936-943.  Back to cited text no. 56      
57.James MF, Latoo MY, Mythen MG, et al. Plasma volume changes associated with two hydroxyethyl starch col­loids following acute hypovolaemia in volunteers. Ana­esthesia 2004; 59: 738-742.  Back to cited text no. 57      
58.Ickx BE, Bepperling F, Melot C, Schulman C, Van der Linden PS. Plasma substitution effects of a new hydroxyethyl starch HES 130/0.4 compared with HES 200/0.5 during and after extended acute normovolaemic haemodilution. Br JAnaesth 2003; 91: 196-202.  Back to cited text no. 58      
59.Jungheinrich C. The starch family: are they all equal? Pharmacokinetics and pharm acodynam ics of hydroxyethyl starches. Transfus Altem Transfus Ivied 2007; 9:152-163.  Back to cited text no. 59      
60.Gandhi SD, Weiskopf RB, Jungheinrich C, et al. Volume replacement therapy during major orthopedic surgery using Voluven® (hydroxyethyl starch 130/0.4) or hetastarch. Anesthesiology 2007; 106: 1120-1127.  Back to cited text no. 60      
61.Ertmer C, Rehberg S, VanAkenH, Westphal M. Relevance of non-albumin colloids in intensive care medicine. Best PractRes ClinAnaesthesiol 2009; 23:193-212.  Back to cited text no. 61      
62.Boldt J. Saline versus balanced hydroxyethyl starch: does it matter? Curr OpinAnaesthesiol 2008; 21: 679-683.  Back to cited text no. 62      


  [Table 1], [Table 2]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
    Article Tables

 Article Access Statistics
    PDF Downloaded3411    
    Comments [Add]    

Recommend this journal