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 blood, thereby enhanc- are likely to have increased permeability, resus- ing its water retaining capacity. citation is best achieved with crystalloids.12 In other circumstances-such as during major Crystalloid versus colloid controversy elective surgery-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- burns, severe sepsis, and cardiopulmonary ate fluids should be used in adequate volumes. bypass.' Colloid solutions 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 saline 0-78 Correspondence to: T, =tissue colloid osmotic pressure Hartmann's solution 0-88 Miss Huskisson. 650 Huskisson Table 3 Chemical basis and source of clinically important colloids Table 5 Molecular weight definitions Natural Hydroxyethyl Gelatins Dextrans 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 Carbohydrate Protein Carbohydrate Source Blood Amylopectin Bovine collagen Bacterial synthesis total mixture's weightxweight of the molecule Examples Albumin Hespan Gelofusine Dextran 40 FFP Pentastarch Haemaccel Dextran 70 Number average molecular weight (M) Pentafraction Excretion Liver/ Amylase/RES/ Kidneys M -mass of the sample in grams kidneys kidneys Proteases n total number of chains FFP, fresh frozen plasma; 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 shock.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 sodium 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 plasmapheresis. 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 urea-linked gelatin.