COLLOIDS
Synthetic colloids : an overview
This article provides a scientific overview of synthetic colloids including tetrastarches and gelatin
Anders Perner MD PhD Department of Intensive Care , Copenhagen University Hospital , Denmark
Colloid solutions are fluids for intravenous use containing large 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 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 article provides an overview of synthetic colloids ( HES and gelatin solutions ), with regard to characteristics , effects , side-effects and their potential role as volume expanders in critical care medicine .
HES Hydroxyethyl starches were the most commonly used colloid solution world-wide according to a 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 hydroxyethylation . HES 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 starches were 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 after HES treatment , including risk of renal and haemostatic impairment , tissue deposition and persistent itching . Consequently , new generations of HES were developed , with lower molecular weights and lower substitution ratios , allowing for a faster elimination from the circulation . Over time , the tetrastarches ( HES with molecular weight 130 kDa and substitution ratio ranging from 0.38 to 0.45 ) have been preferred in various carrier solutions . Similar to earlier HES products , the tetrastarches did not undergo largescale 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
Evidence from systematic reviews Several systematic reviews have investigated the effects of HES versus other fluids on patientimportant outcome measures 7 – 10 ( Table 1 ). The results are quite homogenous even though there are
TABLE 1
Characteristics and results of recent high-quality meta-analyses 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
Comparators Any crystalloid Any fluid except HES 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
hospitalpharmacyeurope . com | 2019 | 7