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Crystalloids and hydroxyethyl starches in noncardiac surgical patients

Colomina, Maria J.; Basora, Misericordia; Moral, Vicky; Llau, Juan V.

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European Journal of Anaesthesiology: January 2017 - Volume 34 - Issue 1 - p 28-29
doi: 10.1097/EJA.0000000000000464
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We are writing in reference to the study by Raiman et al.1 on the use of hydroxyethyl starch (HES) colloids and crystalloids in surgical patients. First, we congratulate the authors on their article, which deals with a subject that is of considerable current interest. Our working group has recently published a set of clinical practice guidelines for the choice of perioperative volume-restoring fluid in adults undergoing noncardiac surgery.2 We agree that there are insufficient data to determine whether there are differences in outcome associated with the use of crystalloids or HES in elective noncardiac surgery. Still, we would like to comment on certain points of interest regarding the authors’ study.

As the authors mention, perioperative fluid therapy has undergone enormous changes in clinical practice over the last few years.3 More restrictive protocols have been adopted to minimise the postoperative complications associated with liberal fluid administration, and it has become evident that the conclusions obtained in studies of critically ill patients cannot necessarily be applied to surgical patients.1,4 Hence, the need to generate additional evidence in this specific population, as was advocated in our guidelines.2

Another important aspect is the lack of studies comparing HES or tetrastarches with the other available fluids (e.g. gelatins, albumin and other starches) in addition to crystalloids. The authors rightly undervalue the existing studies in this area and mention that the meta-analyses assume that the comparator fluids are equally well related to surgical patient outcome.1 They also point out the limitations of comparative studies between crystalloids and other fluids commonly used in regular clinical practice such as albumin and modified gelatins.5,6 To overcome these limitations and decrease the bias implied by the heterogeneity of the different fluids in the comparisons, we excluded studies and systematic reviews published before 2000, since they could include products that have been removed from the market or are now only marginally used. Furthermore, they do not include the more recently available solutions.

The authors included various studies using second-generation HES in their systematic review (including around 120 patients) whereas it may be more appropriate to consider each type of HES as a different colloid. The important characteristics of these solutions may differ (molecular weight, molar substitution ratio and C2/C6 ratio) and confer different clinical effects (expansion capacity and intravascular retention time), which could lead to varying side-effects. Furthermore, evaluators and patients were not adequately blinded in these studies and the number of participants in each was small, which contrasts with the situation in studies in critically ill patients. The authors also included studies performed in cardiac surgery, whereas this population group requires special management regarding volume replacement and should not be evaluated in conjunction with patients undergoing other types of surgery.

We felt it was important to exclude patients undergoing cardiac surgery in our guidelines and included only third-generation HES solutions to avoid the elevated risk of bias. We attempted to specifically answer two questions. The first was ‘What type of fluid (colloids or crystalloids) has the best safety profile for volume replacement during perioperative surgery in procedures other than cardiac surgery?’. The response obtained after Grading of Recommendations Assessment, Development and Evaluation analysis of the available evidence (5320 references, 11 studies selected and 759 patients) was that fluid therapy with crystalloids should be used rather than colloids, with a weak recommendation in their favour (low-quality evidence) because the studies did not show differences between the use of colloids or crystalloids for critical outcomes such as mortality, renal function impairment and coagulation disorder, among others. The second question was ‘What colloid solution (albumin, gelatin, HES 130/04/6% derived from corn, or HES 130/042/6% derived from potato) has the best safety profile for perioperative volume replacement in noncardiac surgery?’. The available evidence suggests the use of HES (HES 130/0.42 or HES 130/0.4) or modified gelatin rather than albumin, with a weak recommendation in their favour (low-quality evidence). Also in this case, the studies did not show differences between the various colloids used in the critical outcomes mentioned. The quality of the evidence was low and the cost of albumin is much higher than that of the remaining colloids; hence, a weak recommendation was formulated in favour of using HES or gelatin over albumin.

To achieve definite conclusions regarding both these questions, we need further well designed clinical trials with large sample sizes evaluating critical outcomes, as well as studies evaluating the cost-effectiveness of these interventions. In the interim, perioperative fluid therapy for noncardiac surgery patients should be based on crystalloids and in situations where a patient refractory to crystalloid bolus therapy requires haemodynamic stabilisation, a third-generation HES or modified gelatin fluid would be recommended.

To sum up, although we agree with Raiman et al. that there are currently insufficient data to determine the full side-effects of HES in noncardiac surgery patients, our findings suggest that they can be safely used instead of gelatins or albumin when needed. In general, however, perioperative volume-restoring fluid therapy should be based on crystalloids.

Acknowledgements relating to this article

Assistance with the letter: none.

Financial support and sponsorship: none.

Conflicts of interest: none.


1. Raiman M, Mitchell CG, Biccard BM, et al. Comparison of hydroxyethylstarch colloids with crystalloids for surgical patients: a systematic review and meta-analysis. Eur J Anaesthesiol 2016; 33:42–48.
2. Basora M, Colomina MJ, Moral V, et al. Clinical practice guide for the choice of perioperative volume-restoring fluid in adult patients undergoing noncardiac surgery. Rev Esp Anestesiol Reanim 2015; 63:29–47.
3. Brandstrup B, Tønnesen H, Beier-Holgersen R, et al. Effects of intravenous fluid restriction on postoperative complications: comparison of two perioperative fluid regimens: a randomized assessor-blinded multicenter trial. Ann Surg 2003; 238:641–648.
4. Moral V, Aldecoa C, Asuero MS. Tetrastarch solutions: are they definitely dead? Br J Anaesth 2013; 111:324–327.
5. Jin SL, Yu BW. Effects of acute hypervolemic fluid infusion of hydroxyethyl starch and gelatin on hemostasis and possible mechanisms. Clin Appl Thromb Hemost 2010; 16:91–98.
6. Parker MJ, Griffiths R, Boyle A. Preoperative saline versus gelatin for hip fracture patients; a randomized trial of 396 patients. Br J Anaesth 2004; 92:67–70.
© 2017 European Society of Anaesthesiology