sign in sign up
<<
Home , Dextran 70, Hydroxyethyl starch, Saline (medicine)

A,vchives ofDisease in Childhood 1992; 67: 649-653 649

;URRENT TOPIC Arch Dis Child: first published as 10.1136/adc.67.5.649 on 1 May 1992. Downloaded from Intravenous volume replacement: which fluid and why?

Lucinda Huskisson

Fluids available for intravenous volume replace- The interstitial space fills more readily after ment may be either crystalloid or colloid. The crystalloid resuscitation. Because of this, the fundamental differences between these fluids volume of fluid required is two to three times are their effects on the Starling equation (table greater than when using colloids, resulting in an 1) which describes fluid flux between the increased risk of tissue oedema. Sponsors of the intravascular and interstitial spaces. Starling crystalloid school maintain that this is not stated that the rate of fluid movement into or harmful despite the fact that tissue oedema has out of a capillary is related to the net hydrostatic been associated with tissue hypoxia and has pressure minus the net colloid osmotic pressure.1 been implicated in delayed healing of bowel The Starling equation has been modified to anastomoses." Despite the increased volumes include coefficients which represent the per- required, crystalloid resuscitation is cheaper meability of the capillary membrane to small than the colloid equivalent (table 2). solutes (Kfc) and its ability to prevent large Velanovich analysed the mortality data from a molecules such as plasma proteins from crossing number of clinical trials and concluded that it (oc).' Colloids may be used to replenish the after trauma, or in instances when the capillaries oncotic strength of the , thereby enhanc- are likely to have increased permeability, resus- ing its retaining capacity. citation is best achieved with crystalloids.12 In other circumstances-such as during major Crystalloid versus colloid controversy elective -mortality rates may be re- Colloids are widely used in Europe for volume duced by using colloids. replacement, while crystalloids are the fluids of The most appropriate resuscitation regimens choice in many centres in the USA,3 but the undoubtedly involve the use of both crystalloids relative merits of the two methods of manage- and colloids. Criteria for volume administration ment remain controversial.4 5 include tachycardia, hypotension, low filling http://adc.bmj.com/ Workers in favour of colloids insist that the pressures, reduced urine output, metabolic intravascular colloid osmotic pressure must be acidosis and increasing core-peripheral temper- kept either above the capillary hydrostatic ature gradient, although it should be remem- pressure or at least greater than 10 mm Hg in bered that a child can maintain a normal heart critically ill patients to avoid a poor rate and systemic blood pressure despite a 25% prognosis.' 7 Proponents of crystalloids main- loss of circulating volume. Volume administra-

tain that colloids leak out of the capillaries, tion should not be based on reflex prescribing- on September 29, 2021 by guest. Protected copyright. increasing interstitial colloid osmotic pressure 'He looks volume depleted, therefore give 10 which has a detrimental effect by increasing ml/kg of plasma'. An individual patient's fluid fluid flux out of the capillary.8 This is more requirements should be based on the aetiology likely to occur if oic is reduced, as happens after of the volume depletion, and the most appropri- , severe , and cardiopulmonary ate fluids should be used in adequate volumes. bypass.' Colloid expand the intravascular space more effectively than crystalloids, with Intravenous fluids available the same increase in cardiac output being CRYSTALLOIDS achieved by smaller volumes and with less (1) Dextrose haemodilution. The crystalloid proponents Because dextrose is rapidly metabolised after argue that the interstitial space is depleted in intravenous administration, 5% or 10% dextrose conditions of hypovolaemia because of fluid solutions act as free water, quickly equilibrating shift into intravascular and intracellular com- partments.'0 Table 2 Cost of volume replacement by various agents Fluid Cost in £ per 500 ml Table I Starling equation 4 5% Albumin 33 00 J,= Kf,[(P, - P,) - a., -Jr,)] 20% Albumin (100 ml) (37-00) Where Hespan 16-72 Nuffield Department of J, =rate of fluid movement into/out of capillary Pentaspan 15 70 Paediatric Surgery, K,, =capillary filtration coefficient Gelofusine 3-56 Institute of Child Health, P, =capillary hydrostatic pressure Haemaccel 3 81 30 Guilford Street, P, =tissue fluid hydrostatic pressure Rheomacrodex 6 51 'London WC1N 1EH (j, =reflection coefficient Macrodex 4-11 jT, =capillary colloid osmotic pressure Normal 0-78 Correspondence to: T, =tissue colloid osmotic pressure Hartmann's 0-88 Miss Huskisson. 650 Huskisson

Table 3 Chemical basis and source of clinically important colloids Table 5 Molecular weight definitions Natural Hydroxyethyl Gelatins Weight average molecular weight (M,,,) starches sum of each molecule's weight Arch Dis Child: first published as 10.1136/adc.67.5.649 on 1 May 1992. Downloaded from Chemical basis Protein Protein Carbohydrate Source Blood Amylopectin Bovine collagen Bacterial synthesis total mixture's weightxweight of the molecule Examples Albumin Hespan Gelofusine 40 FFP Pentastarch Haemaccel Number average molecular weight (M) Pentafraction Excretion Liver/ /RES/ Kidneys M -mass of the sample in grams kidneys kidneys Proteases n total number of chains FFP, ; RES, reticuloendothelial system. After Hulse and Yacobi.'5

between the intracellular and extracellular fluid table 4 summarises the pharmacology. The two compartments. For every 100 ml infused, only molecular weights quoted for synthetic colloids 7-5 ml will remain in the intravascular space for are defined in table 5. The weight average a useful period of time, so dextrose solutions molecular weight (Mw) determines the viscosity, are inappropriate for intravascular fluid resusci- while the number average molecular weight tation. (M ) gives an indication of the osmotic pressure exerted by the fluid. Albumin is monodisperse- that is, all of the molecules within a solution are (2) Isotonic crystalloid solutions the same size and both M, and M are 69 000. Isotonic crystalloids (for example, normal saline All of the synthetic colloids are polydisperse, and Hartmann's solution) equilibrate rapidly and have different values for Mw and M (table throughout both the interstitial and intravascular 4). spaces, so approximately one quarter of the administered volume will remain within the intravascular space. PHARMACOLOGY OF INDIVIDUAL COLLOIDS Natural colloids (A) Fresh frozen plasma-fresh frozen plasma is (3) Hypertonic saline solutions extracted from donated blood and because it is These have shown a resurgence of popularity. unpasteurised it has the potential to transmit Small volumes of 7-5% saline have successfully blood borne infections. The Consensus Con- maintained the circulation after hypovolaemic ference held at the National Institutes of Health .13 14 Their role in paediatrics has not yet has laid down strict guidelines for the adminis- been assessed, and hypertonic saline may prove tration of fresh frozen plasma, concluding that inappropriate for neonates with immature there is no justification for its use as a volume handling.'5 expander. 19

(B) Albumin-Human albumin solution is http://adc.bmj.com/ COLLOID SOLUTIONS derived from donated blood by fractionation Colloid solutions, both natural (for example, and/or . It is produced as a 4-5% human albumin solutions) and the synthetic solution (iso-oncotic with plasma) or as more macromolecules (for example, the gelatins, concentrated (hyperoncotic) 10% or 20% solu- hydroxyethyl starches, and dextrans), theor- tions of 'salt poor' albumin.20 etically remain within the intravascular space. Albumin persists within the body for about

Thus, volume for volume, they provide a 20 days, although its duration of action within on September 29, 2021 by guest. Protected copyright. greater and more sustained haemodynamic the intravascular compartment varies from less response than crystalloids. In the UK, standard than two hours to more than a day.2' paediatric practice is to use natural colloids for Although freely donated, the processing of resuscitation. Although synthetic colloids are human albumin is expensive (table 2). used sporadically, there has been a reluctance to use them routinely because of a lack of clinical trials concerning their use in children. Synthetic colloids (A) Gelatins-The gelatins tend to be considered as a homogeneous group but, because of dif- BASIC STRUCTURE OF COLLOIDS ferent manufacturing processes,22 the individual The chemical basis and source of the clinically solutions have differing properties, particularly important colloids are shown in table 3, and in the incidence of adverse reactions. The new

Table 4 Characteristics of various colloids"' 1617 Albumin Gelofusine Haemaccel Hetastarch Tentastarch Dextran 40 Dextran 70 M,, (kDa) 69 30 35 450 200 40 70 M (kDa) 69 22 5 24 5 71 35 25 39 Soziium (mmol/l) 130-160 154 145 154 154 154 154 Potassium (mmol/l) 1 <04 5-1 0 0 0 0 Calcium (mmol/l) 0 <0 4 12-5 0 0 0 0 Duration of action (hours) 6 3-4 3-4 >8 6-8 3-4 6-8 Survival in body (days) 21 7 7 2-65 7 6 2842 Water binding (ml H20/g colloid) 18 42-8 41 7 20 30 37 29 Intravenous volume replacement: which fluid and why? 651

generation gelatins are widely used within 0-05% respectively) and the former has been Europe. In the UK the two most commonly associated with free di-isocyanate, which causes used solutions are: (1) Gelofusine (B Braun) histamine release; and secondly, the incidence Arch Dis Child: first published as 10.1136/adc.67.5.649 on 1 May 1992. Downloaded from which is a 'modified fluid' or succinylated gela- of allergic reactions can be reduced by pre- tin and (2) Haemaccel (Hoechst) which is a treatment with HI and H2 blockers.33 polygeline, or -linked gelatin. The overall incidence of anaphylactoid re- For intravascular volume expansion, they actions to HES is quoted at 0-08%, the majority produce an effect which is almost equivalent to of which are mild, although severe reactions albumin, with a duration of action of three to have been reported.34 four hours. In vitro evidence suggests that in The dextrans elicit the worst reactions, both conditions associated with capillary leak, Gelo- in incidence and severity. These are mediated fusine may be more efficacious than albumin.23 by dextran reactive antibodies which trigger the release of vasoactive mediators,33 and can be (B) Hydroxyethyl starches (HES)-HES are reduced by pretreatment with a hapten. The derived from amylopectin which is stabilised by incidence of cardiac arrest associated with the hydroxyethylation to prevent rapid hydrolysis dextrans, together with their adverse effects on by amylase. The HES solutions show a dis- haemostasis and interference with the cross crepancy between Mw and M (table 4) because matching of blood are the main factors in their they contain molecules with a wide range of unpopularity. molecular weights, the smallest of which will be rapidly excreted by the kidneys, with the largest being taken up by macrophages of the reti- (2) effects culendothelial system. The greater the degree of Dilutional effects are seen with all the colloids substitution by hydroxyethyl groups, the more (except fresh frozen plasma) but the polysac- resistent the molecule is to breakdown by charides have been associated with abnormalities amylase and, therefore, the longer the survival of haemostasis which are more than simply within the body and the circulation. dilutional. In particular, factor VIII concentra- Of the available HES solutions, the highest tions may be appreciably reduced.35 Although degree of substitution (seven hydroxyethyl in vitro tests may be altered by HES, the effects groups per 10 of ) is seen in hetastarch are rarely of clinical significance3138 unless (Hespan, Du Pont). Its intravascular effect massive volumes are infused.39 The coagulation may last up to 24 hours and its survival within effects of the dextrans are more pronounced, the body is between two and more than 60 and the dextrans are therefore used to reduce days. 8 24 25 the incidence of postoperative venous throm- Pentastarch (Pentaspan, Du Pont) has recently bosis and fatal pulmonary embolism.40 As these received a product licence in the UK. It has five complications are exceedingly rare in general groups per 10 of glucose. Although it still paediatric surgery, they do not provide an

contains a large range of molecular sizes, it does indication for the use of dextrans in infants and http://adc.bmj.com/ not include molecules with a weight greater children, although dextran 40 is used in the than a million daltons. This gives the compound postoperative period after orthotopic liver the advantage of a shorter persistence within the transplantation in an attempt to reduce throm- body, but with a similar efficacy to heta- botic complications in the anastomosed vessels.4' starch.26 27 By diafiltering pentastarch, all of the mole- cules with a of less than 100 000 daltons can (3) Risks of infection

Mw on September 29, 2021 by guest. Protected copyright. be removed. This fluid (Pentafraction) is not The albumin solutions used in the UK are pre- commercially available, but preliminary animal pared from donated blood which is screened for work has suggested that its use may be associated antibodies to certain blood borne diseases. with a reduction in capillary leak.9 28 29 Because recently infected donors may carry a virus against which antibodies may not yet have (C) Dextrans-Because of their high incidence been raised, the potential for infection (for ofadverse effects, the dextrans are inappropriate example, with HIV or the hepatitis viruses) for volume expansion in paediatrics. The two remains should the pasteurisation process fail. most commonly encountered dextrans are dextran 40 (for example, Rheomacrodex, Pharmacia) and dextran 70 (for example Macrodex, Pharmacia), the number representing (4) Interference with laboratoty investigations the Mw. The polysaccharides may interfere with cross matching reactions and estimations of the erythrocyte sedimentation rate by 'coating' the ADVERSE EFFECTS OF COLLOIDS red cells and causing their aggregation. The (1) Anaphylactoid reactions effects of HES can be reversed by washing These have been reported with both natural30 the cells with saline. The effects of dextran are and synthetic3' colloids. The reactions may be long lasting, which is a major disadvantage in mild/moderate or severe as classified by Ring patients requiring blood after dextran adminis- and Messmer,32 and the precise causes of the tration. reactions remain unclear. Release of histamine The dextrans have caused false positive by the gelatins has been suggested: firstly, glucose analysis results,42 and, together with because the incidence is higher with urea linked Haemaccel, may interfere with the biuret deter- rather than succinylated gelatins (0 1% and mination of serum total protein.43 The gelatins 652 Huskisson

migrate within the a2-fraction in electrophoresis, Conclusions but do not appear to affect immunological Although there are certain indications for assays.42 natural colloids-for example, after certain Amylase contributes to the elimination of open heart operations when massive colloid Arch Dis Child: first published as 10.1136/adc.67.5.649 on 1 May 1992. Downloaded from HES from the body, and the serum amylase infusion may be required, synthetic colloids value may double after HES infusion.' could often be given in their place. Because of their safety, the gelatins (particularly the modi- fied fluid gelatins) are the most appropriate CLINICAL STUDIES WITH SYNTHETIC COLLOIDS choice but there are situations when the superior There is a wealth of literature describing the plasma expansion of hydroxyethyl starches may adult experience with synthetic colloids, and a be required. Although studies with synthetic corresponding paucity of paediatric studies. colloids in adult patients may be extrapolated to Boon has published his experience with the paediatric population, there remains a need Haemaccel over 14 years in more than 8000 for an evaluation of synthetic colloids in pae- patients,45 whilst Lundsgaard-Hansen and diatric practice. Tschirren46 have reported 20 years experience with Gelofusine. Both papers conclude that 1 Starling EH. On the absorption of fluids from the connective these two fluids are safe, effective, and worth- tissue spaces. .7 Physiol 1896;19:312-26. while fluids for volume replacement. In criti- 2 Bevan DR. Colloid osmotic pressure. Anaesthesia 1980;35: 263-70. cally ill patients, Gelofusine has been associated 3 Shoemaker WC. Hemodynamic and oxygen transport effects with increased oxygen consumpton.47 of crystalloids and colloids in critically ill patients. Curr Stud Hematol Blood Transfus 1986;53:155-76. Six per cent HES was equal to albumin 4 Laks H, O'Connor NE, Anderson W, et al. Crystalloid versus for peroperative volume replacement during colloid hemodilution in man. Surg Gynecol Obstet 1976;142: 506-12. paediatric anaesthesia.4" HES has been used 5 Poole GV, Meredith JW, Pennell T, et al. Comparison of satisfactorily in the pump prime for bloodless colloids and crystalloids in resuscitation from hemorrhagic shock. Surg Gynecol Obstet 1982;154:577-86. open heart surgery in children who are Jehovah's 6 Weil MH, Henning RJ, Morissette MP, et al. Relationship Witnesses.49 It has been studied extensively in between colloid osmotic pressure and pulmonary artery wedge pressure in patients with acute cardiorespiratory adults with the conclusion that there is no failure. Am J Med 1978;64:643-50. difference between HES and albumin, with 7 Falk JL, Rackow EC, Astiz M, et al. Fluid resuscitation in shock. Journal of Cardiothoracic Anesthesia 1988;2 Suppl: HES offering a considerable cost saving.36 50-52 33-8. Despite their unacceptable level of adverse 8 Virgilio RW, Rice CL, Smith DE, et al. Crystalloid versus colloid resuscitation: is one better? A randomized clinical effects, there is little doubt that the dextrans are study. Surgery 1979;85:129-39. very efficient plasma expanders.33 -5 9 Zikria BA, King TC, Stanford J, et al. A biophysical approach to capillary permeability. Surgery 1989;105: 625-31. 10 Ross AD, Angaran DM. Colloids versus crystalloids-a continuing controversy. Drug Intelligence and Clinical PRESCRIBING PITFALLS Pharmacy 1984;18:202-14. (1) Serum albumin and measurement of colloid 11 Chan STF, Kapadia CR, Johnson AW, et al. Extracellular osmotic pressure fluid volume expansion and third space sequestration at the site of small bowel anastomoses. Br3J Surg 1983;70:36-9. http://adc.bmj.com/ Under normal conditions, only half of the 12 Velanovich V. Crystalloid versus colloid fluid resuscitation: a meta-analysis of mortality. Surgery 1989;105:65-71. body's endogenous albumin is intravascular, 13 de Felippe J, Timoner J, Velasco IT, et al. Treatment of but it contributes about 80% of the intravascular refractory hypovolaemic shock by 7 5% sodium injections. Lancet 1980;ii:1002-4. colloid osmotic pressure.56 In critically ill 14 Vincent J-L. Fluids for resuscitation. Br3' Anaesth 1991;67: patients, because of the 'acute phase reaction', 185-93. 15 Krummel TM, Lloyd DA, Rowe MI. The postoperative the serum albumin concentrations may not pro- response of the term and preterm newborn infant to sodium vide an accurate reflection of the colloid osmotic administration. J Pediatr Surg 1985;20:803-9.

16 Klotz U, Kroemer H. Clinical pharmacokinetic considerations on September 29, 2021 by guest. Protected copyright. pressure as the production of acute phase pro- in the use of plasma expanders. Clin Pharmacokinet teins takes precedence over the synthesis of 1987;12: 123-35. 17 Lutz H, Georgieff M. Effects and side effects of colloid albumin.57 Albumin may be administered not plasma substitutes as compared to albumin. Curr Stud because volume replacement is required, but Hematol Blood Transfus 1986;53:145-54. 18 Hulse JD, Yacobi A. Hetastarch: an overview of the colloid because the serum albumin concentration is and its metabolism. Drug Intelligence and C'linical Pharmacy low. 1983;17:334-41. 19 National Institutes of Health. Fresh frozen plasma. Indi- cations and risks. JAMA 1985;253:551-3. 20 McClelland DBL. Human albumin solutions. BMJ 1990; (2) Inadequate resuscitation 300:35-7. 21 Lewis RT. Albumin: role and discriminative use in surgery. Problems with crystalloid resuscitation are often CanJ Surg 1980;23:322-8. related to inadequate volumes being adminis- 22 Saddler JM, Horsey PJ. The new generation gelatins. A review of their history, manufacture and properties. tered, because the prescriber fails to allow for Anaesthesia 1987;42:998-1004. fluid movement into the interstitial compart- 23 Webb AR, Barclay SA, Bennett ED. In vitro colloid osmotic pressure of commonly used plasma expanders and substi- ment. tutes: a study of the diffusibility of colloid molecules. Intensive Care Med 1989;15:116-20. 24 Thompson W, Fukushima T, Rutherford RB. Intravascular persistence, tissue storage and excretion of hydroxyethyl (3) Volume overload starch. Surg Gynecol Obstet 1970;131:965-72. While the gelatins are plasma substitutes, and 25 Yacobi A, Stoll RG, Sum CY, et al. of hydroxyethyl starch in normal subjects. J Clin Pharmacol can be used interchangeably with albumin, the 1982;22:206-12. dextrans and hydroxyethyl starches are true 26 Mishler JM, Parry ES, Sutherland BA, et al. A clinical study of low molecular weight hydroxyethyl starch, a new plasma plasma expanders-that is, they produce an expander. Br3' C'lin Pharmacol 1979;7:619-22. increase in plasma volume greater than the 27 Waxman K, Holness R, Tominaga G, et a!. Hemodynamic and oxygen transport effects of Pentastarch in volume of colloid infused. Although this may be resuscitation. Ann Surg 1989,209:341-5. of clinical benefit, the risk of fluid overload and 28 Zikria BA. Subbarao C, Oz MC, et a!. Macromolecules reduce abnormal microvascular permeability in rat limb significant haemodilution is greater when ischemia-reperfusion . C,rit C^are Med 1989;17: administered by unwary prescribers. 1306-9. Intravenous volume replacement: whichfluid and why? 653

29 Webb AR, Tighe D, Moss RF, et al. Advantages of a narrow- 44 Condit D, Freeman K, Brodman R. Hyperamylasemia in range, medium molecular weight hydroxyethyl starch for cardiac surgical patients receiving hydroxyethyl starch. volume maintenance in a porcine model of fecal peritonitis. Journal of C'ritical Care 1987;2:36-8. Crit Care Med 1991;19:409-16. 45 Boon P. Clinical use of polygelatin. Dev Biol Stand 1981;48:

30 Ring J, Stephan W, Brendel W. Anaphylactoid reactions to 193-7. Arch Dis Child: first published as 10.1136/adc.67.5.649 on 1 May 1992. Downloaded from infusions of plasma protein and human serum albumin. 46 Lundsgaard-Hansen P, Tschirren B. Clinical experience with Clin 1979;9:89-97. 120,000 units of modified fluid gelatin. Dev Biol Stand 31 Ring J. Anaphylactoid reactions to plasma substitutes. Int 1981 ;48:25 1-6. Anesthesiol Clin 1985;23:67-95. 47 Edwards JD, Nightingale P, Wilkins RG, et al. Hemodynamic 32 Ring J, Messmer K. Incidence and severity of anaphylactoid and oxygen transport response to modified fluid gelatin in reactions to colloid volume substitutes. Lancet 1977;i: critically ill patients. Crit Care Med 1989;17:996-8. 466-9. 48 Hausdorfer J, Hagemann H, Heine J. Comparison of plasma 33 Messmer K. Characteristics, effects and side-effects of plasma substitutes human albumin 5% and hydroxyethyl starch 6% substitutes. In: Lowe KC, ed. Blood substitutes: preparation, (40,000. 0.5) in paediatric anaesthesia. Anasth Intensivther physiology and medical applications. Chichester: Ellis Notfalimed 1986;21:137-42. Horwood Series in Biomedicine, 1988:51-70. 49 Kawaguchi A, Bergsland J, Subramanian S. Total bloodless 34 Cullen MJ, Singer M. Severe anaphylactoid reaction to open heart surgery in the pediatric age group. C'irculation hydroxyethyl starch. Br3J Anaesth 1990;45:1041-2. 1984;70 suppl 1:30-7. 35 Strauss RG. Review of the effects of hydroxyethyl starch on blood coagulation system. Transfusion 1981;21:299-302. 50 Diehl JT, Lester JL III, Cosgrove DM. Clinical comparison 36 Munsch CM, Maclntyre E, Machin SJ, et al. Hydroxyethyl ofHetastarch and albumin in postoperative cardiac patients. starch: an alternative to plasma for postoperative volume Ann Thor Surg 1982;34:674-9. expansion after cardiac surgery. BrJ3 Surg 1988;75:675-8. 51 Kirklin JK, Lell WA, Kouchoukos NT. Hydroxyethyl starch 37 Falk JL, Rackow EC, Astiz ME, et al. Effects of hetastarch versus albumin for colloid infusion following cardio- and albumin on coagulation in patients with . pulmonary bypass in patients undergoing myocardial J Clin Pharmacol 1988;28:412-5. revascularization. Ann Thor Surg 1984;37:40-6. 38 Gold MS, Russo J, Weinhouse G, et al. Comparison of 52 Lumb PD. A comparison between 25% albumin and 6% hetastarch to albumin for perioperative in patients hydroxyethyl starch on lung water accumulation during undergoing abdominal aortic aneurysm surgery. A prospec- and immediately after cardiopumonary bypass. Ann Surg tive, randomised study. Ann Surg 1990;21:482-5. 1987;206:2 10-3. 39 Lockwood DNJ, Bullen C, Machin SJ. A severe 53 Lamke L-O Liliedahl S-0. Plasma volume changes after following volume replacement with hydroxyethyl starch in infusion of various plasma expanders. Resuscitation 1976;5: a Jehovah's Witness. Anaesthesia 1988;43:391-3. 93-102. 40 Strauss RG. Volume replacement and coagulation: a com- 54 Karanko MS. Effects of three colloid solutions on plasma parative review. J7ounral ofCardiothoracic Anaesthesia 1988; volume and hemodynamics after coronary bypass surgery. 2 suppl:24-32. Crit Care Med 1987;15:1015-22. 41 Busuttil RW, Seu P, Millis JM, et al. Liver transplantation in 55 Stacca R, Bertellini E, Piccinini P, et al. Plasma expanders in children. Ann Surg 1991;213:48-57. hemorrhagic shock. Resuscitation 1989;18:153-4. 42 Lutz H, Georgieff M. Effects and side effects of colloid 56 Grunert A. Colloid osmotic pressure and albumin metabolism plasma substitutes as compared to albumin. Cur Stud during . Curr Stud Hematol Blood Hematol Blood Transfus 1986;53:145-54. 7ransfus 1986;53:18-32. 43 Weber JA, van Zanten AP. Interference of plasma expanders 57 Lundsgaard-Hansen P. Physiology and pathophysiology of in the determination of total protein. Clin Chem 1989;35: colloid osmotic pressure and albumin metabolism. Curr 2143-4. Stud Hematol Blood Transfus 1986;53: 1-17. http://adc.bmj.com/ on September 29, 2021 by guest. Protected copyright.