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Synthetic colloids


Synthetic colloids


It is clear from several high-quality trials and meta-analyses in critically ill patients that treatment with tetrastarches causes impaired renal function and haemostasis and may even increase mortality. The use of synthetic colloids should be limited in all patient categories


Anders Perner MD PhD Department of Intensive Care, Copenhagen University Hospital – Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark Email: anders.perner@regionh.dk


Colloid solutions are fluids for intravenous use containing larger molecules, which prolong the time they remain in the circulation. The larger molecules used to obtain the colloidal effects are human albumin, which is a plasma protein, or synthetically modified sugars or collagens. The most frequently used synthetic colloid solutions are hydroxyethyl starch (HES) and gelatin. Colloid solutions have been widely used for volume expansion in patients, who are either intravascular depleted of fluid or at risk of becoming so.1


In recent


years, large trials in critically ill patients have assessed the effects and harms of colloids.2–4


The conclusions of these trials


have questioned the overall effects of colloids, detailed their side-effects and the harm induced by these side-effects. In this chapter, I will describe the synthetic colloids, HES and gelatin solutions, with regard to characteristics, effects, side-effects and their potential role as volume expanders in critical care medicine.


Hydroxyethyl starch


Hydroxyethyl starches were the most commonly used colloid solution world- wide according to a recent point prevalence study.1


Table 1: Characteristics and results of recent high-quality meta- analyses on the use of hydroxyethyl starch in critically ill patients Systematic reviews


Cochrane7


HES solution Comparators


Patients


Outcomes Mortality RRT AKI


Any HES solution Any crystalloid


Zarychanski et al8 Any HES solution


Any fluid except HES


RR (95% CI)


Gattas et al9 130/0.38–0.42


Any fluid except HES 130


Critically ill patients Critically ill patients Acutely ill adults RR (95% CI)


RR (95% CI)


1.10 (1.02–1.19) – –


1.09 (1.02–1.17)* 1.32 (1.15–1.50) 1.27 (1.09–1.47)


1.08 (1.00–1.17) 1.25 (1.08–1.44) –


*Excluding trials by Boldt due to possible fraud **Trials with low risk of bias AKI, acute kidney injury; CI, confidence interval; HES, hydroxyethyl starch; RR, relative risk; RRT, renal replacement therapy


hydroxyethylation. Hydroxyethyl starch is degraded by amylase and excreted in the urine, but a substantial part leaves the circulation even in healthy persons, in whom 50% of the infused volume cannot be accounted for at 24 hours.5


The fate of They are derived from 6


either potatoes or maize and characterised by their molecular weight, degree of hydroxyethylation (substitution ratio) and C2:C6 pattern for


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this 50% is unknown, but some of it is likely taken up in tissues, where further degradation is unlikely as amylase is not expressed in most tissues. In the tissues, HES will act as a foreign body. When the first generation of HES was approved for medical treatment many years ago, the solutions had not been adequately tested, as this was not required at that time. After some time, safety concerns were raised, including risk of renal and haemostatic impairment, tissue deposition and persistent itching after HES treatment. Consequently, new generations of HES were developed with lower molecular weights and lower substitution ratios, allowing for a faster elimination from the circulation. In recent decades, HES with molecular weight 130 kDa and substitution ratio


ranging from 0.38 to 0.45, the so-called tetrastarches, have been preferred in various carrier solutions. As for the previous HES products, the tetrastarches did not undergo large-scale clinical testing prior to marketing. The concerns about side-effects continued, in particular in critically ill patients, leading to recommendations against the general use of HES in the intensive care setting.6


We


now know a lot more in the critical care setting, as evidence from the recent high-quality trials has been pooled in high-quality systematic reviews.


Evidence from the systematic reviews on HES in critically ill patients


Several systematic reviews have investigated the effects of HES versus other fluids on patient-important outcome measures7–10


(Table 1). The


results are quite homogenous even though there are differences in the inclusion of trial data regarding HES solutions, comparators and patient


Haase et al10 130/0.38–0.42


Crystalloid or albumin


Sepsis RR (95% CI)


1.11 (1.00–1.23)** 1.36 (1.08–1.72) 1.18 (0.99–1.40)


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