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

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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 worldwide according to a recent point prevalence study . ¹ They are derived from either potatoes or maize and characterised by their molecular weight , degree of hydroxyethylation ( substitution ratio ) and C2 : C6 pattern for

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

Systematic reviews Cochrane ⁷ Zarychanski et al ⁸ Gattas et al ⁹ Haase et al ¹⁰ HES solution Any HES solution Any HES solution 130 / 0.38 – 0.42 130 / 0.38 – 0.42

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 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

Any fluid except HES 130

Crystalloid or albumin

Patients Critically ill patients Critically ill patients Acutely ill adults Sepsis Outcomes RR ( 95 % CI ) RR ( 95 % CI ) RR ( 95 % CI ) RR ( 95 % CI ) Mortality 1.10 ( 1.02 – 1.19 ) 1.09 ( 1.02 – 1.17 )* 1.08 ( 1.00 – 1.17 ) 1.11 ( 1.00 – 1.23 )** RRT – 1.32 ( 1.15 – 1.50 ) 1.25 ( 1.08 – 1.44 ) 1.36 ( 1.08 – 1.72 ) AKI – 1.27 ( 1.09 – 1.47 ) – 1.18 ( 0.99 – 1.40 )

* 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 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 measures ^{7 – 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 www . hospitalpharmacyeurope . com