1Department of Anaesthesia and 2Yorkshire Heart Centre, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, UK
Accepted for publication: June 15, 2000
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Abstract |
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Br J Anaesth 2000; 85: 6969
Keywords: fluids, i.v.; complications, pruritus
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Introduction |
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Many studies have compared different colloids. The variables most often assessed include maintenance of intravascular volume, cardiac function, coagulation variables13 and end-organ function.4 No one colloid has a clinical advantage, despite theoretical and in vitro advantages of one agent over another. Hydroxyethyl starch remains in the intravascular compartment for longer, so it is believed to cause less tissue oedema than other colloids. Some suggest that hydroxyethyl starch molecules can plug leaky capillaries4 and prevent fluid moving from the vessels to the tissues.
Giving hydroxyethyl starch may cause significant and prolonged pruritus.5 We assessed the prevalence and severity of pruritus in patients who had received EloHAES (hydroxyethyl starch 200/0.62) for volume replacement during cardiac surgery, compared with cardiac surgical patients who had not.
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Patients and methods |
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Statistical analyses were performed using the SPSS 8.0 for Windows statistical package. The presence or absence of pruritus in individuals who had received EloHAES was compared with that in the control population using 2 x 2 contingency tables. Fischers exact test was performed, as the expected numbers were too small for 2 results to be accurate. The volume of EloHAES administered was compared between patients with and without pruritus, and then in patients with no, mild, moderate and severe pruritus, using the MannWhitney U-test and KruskalWallis tests, respectively. Two-tailed P values of <0.05 were considered statistically significant.
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Results |
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Discussion |
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Pruritus after administration of hydroxyethyl starch was first reported in a patient undergoing leucophoresis.5 Subsequent reports have demonstrated an association between various hydroxyethyl starches and pruritus. The clinical features vary and skin changes are often absent. The pruritus may be generalized or localized, have a delayed onset of up to several weeks; it may have precipitating factors such as warmth and mechanical irritation.69 The pruritus is frequently persistent, lasting months or even years,10 and is usually refractory to treatment with antihistamines or steroids, although some benefit has been reported with capsaicin,11 hydroxyzine9 12 13 and amantidine.14
Hydroxyethyl starches have hydroxyethyl groups bound to a high molecular weight amylopectin backbone, which delays rapid hydrolysis by plasma -amylase. The main difference between the different hydroxyethyl starch products is in their molecular weights and in the level of substitution with hydroxyethyl groups. The latter is now thought to be the major determinant of pharmacological behaviour.15 16 EloHAES is a medium molecular weight hydroxyethyl starch, with a mean molecular weight of 200 000 Da (80% between 13 700 and 500 000), and has a molar substitution of 0.62, that is every 100 glucose moieties have 62 hydroxyethyl groups attached. The low molecular weight molecules and breakdown products are excreted in the urine, so hydroxyethyl starch solutions are contraindicated in severe chronic renal insufficiency. Hydroxyethyl starches are deposited in various tissues and delayed excretion occurs following metabolism by tissue glucosidases.1725 Skin biopsies from individuals who developed pruritus have shown deposits of hydroxyethyl starch within the intracellular vacuoles of macrophages, Langerhans cells, keratinocytes, vascular endothelium, perineural cells and sweat gland epithelia.6 26 The size and severity of the deposits may depend on the dose and preparation administered.10 Symptomatic improvement can occur as hydroxyethyl starch deposits diminish in size, which may take
3 years.6
A correlation between the volume of hydroxyethyl starch infused and the severity of pruritus has been found.6 10 21 26 27 In one study, the mean dose of hydroxyethyl starch in the group suffering from pruritus was 7.8 g kg1, equivalent to 9.75 litres of EloHAES, compared with 1 litre equivalent in the non-pruritic group.21 Individuals given 150 g of hydroxyethyl starch in another study had a 1% incidence of pruritus, which increased by 5.5% with each additional 50 g dose.26 The incidence of pruritus associated with Pentastarch in an intensive care population28 was slightly higher than that found in the present study. This was possibly because a greater volume of starch was administered. A similar proportion also suffered severe pruritus, although not defined, with a comparable duration to our study. We were unable to demonstrate a correlation between dose and response in our study, either because we used less starch, or because the smaller range of doses administered may not have had sufficient power to detect a correlation. One study failed to demonstrate an increase in pruritus in a group receiving hydroxyethyl starch when compared with a group receiving lactated Ringers solution.29 The volumes of hydroxyethyl starch in that study were much smaller (around 650 ml in total) than those in other studies where pruritus was found, suggesting that there may be a threshold dose for pruritus to occur. Cox and Popple suggested that metabolic polymorphism could be responsible for abnormal handling of hydroxyethyl starches, thus predisposing certain patients to larger tissue deposits of hydroxyethyl starch.7 This could help to explain why in our study some patients developed pruritus and others did not, despite similar volumes of starch administered.
We found that 22% of cardiac surgical patients who received EloHAES suffered from pruritus, often with sufficient severity to interfere with their daily routine. Our findings support previous work that has linked administration of other hydroxyethyl starches with pruritus. As EloHAES contains the same basic molecular structure as other hydroxyethyl starch solutions, we propose that the mechanism of pruritus is similar.10 27 Many hydroxyethyl starches can cause long-term pruritus, and this should be considered in the choice of volume replacement therapy.
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Acknowledgements |
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Footnotes |
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References |
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