Research Article: Hydroxyethyl starch for volume expansion after subarachnoid haemorrhage and renal function: Results of a retrospective analysis

Date Published: February 15, 2018

Publisher: Public Library of Science

Author(s): Sven Bercker, Tanja Winkelmann, Thilo Busch, Sven Laudi, Dirk Lindner, Jürgen Meixensberger, Johannes Boltze.


Hydroxyethyl starch (HES) was part of “triple-H” therapy for prophylaxis and therapy of vasospasm in patients with subarachnoid haemorrhage (SAH). The European Medicines Agency restricted the use of HES in 2013 due to an increase of renal failure in critically ill patients receiving HES compared to crystalloid fluids. The occurrence of renal insufficiency in patients with SAH due to HES is still uncertain. The purpose of our study was to evaluate whether there was an association with renal impairment in patients receiving HES after subarachnoid haemorrhage.

Medical records of all non-traumatic SAH patients treated at the Departments of Anaesthesiology and Neurosurgery, University Hospital of Leipzig, Germany, between January 2009 and December 2014 were analysed. Patients received either HES 6% and/or 10% (HES group, n = 183) or exclusively crystalloids for fluid therapy (Crystalloid group, n = 93). Primary outcome was the incidence of acute kidney injury.

The study groups had similar characteristics except for initial SAPS scores, incidence of vasospasm and ICU length of stay. Patients receiving HES fulfilled significantly more often SIRS (systemic inflammatory response syndrome) criteria. 24.6% (45/183) of the patients in the HES group had acute kidney injury (KDIGO 1–3) at any time during their ICU stay compared to 26.9% (25/93) in the crystalloid group (p = 0.679). Only few patients needed renal replacement therapy with no significant difference between groups (Crystalloid group: 4.3%; HES group: 2.2%; p = 0.322). The incidence of vasospasm was increased in the HES group when compared to the crystalloid group (33.9% vs. 17.2%; p = 0.004).

In the presented series of patients with non-traumatic SAH we found no significant association between HES therapy and the incidence of acute kidney injury. Treatment without HES did not worsen patient outcome.

Partial Text

About 43% of patients suffer from symptomatic vasospasm following subarachnoid haemorrhage (SAH) and 34% of these keep long-term disabilities [1]. Vasospasm leads to a substantial increase in morbidity and mortality after SAH. It has been estimated that vasospasm is causing 23% of deaths in patients with SAH [2]. Although the mechanism leading to narrowing of cerebral arteries after SAH has been the subject of extensive research, highly effective therapeutic or prophylactic treatments are still lacking. Efforts have been focused on improvement of regional blood flow by altering haemodynamics. Hence, “triple-H” therapy (hypervolaemia, hypertension, haemodilution) was established aiming at preventing cerebral infarction by improving perfusion [3]. To achieve effective and long-term plasma expansion, artificial colloids such as hydroxyethyl starch (HES) have been used in the past but the effects on regional blood flow and outcome remained controversial [4]. Since there is no substantial evidence supporting this concept instead of euvolaemia, current guidelines, however, do not recommend hypervolaemia anymore [5].

Patients were identified by selecting SAH as primary diagnosis in the hospital information system (SAP SE, Walldorf Germany). Clinical data of these patients were analysed retrospectively using the computer-based patient data management system (COPRA System GmbH, Berlin, Germany). The local ethics committee approved the study and waived the need for informed consent.

Between January 2009 and December 2014 16,348 patients have been treated in the interdisciplinary surgical ICU at the University Hospital of Leipzig. A primary diagnosis of SAH was documented in 276 patients. Out of these, n = 183 received HES (HES group; n = 106 with HES 6% and/or HES 10%; n = 77 with only HES 6%) whereas n = 93 were treated only with crystalloids as volume therapy (Crystalloid group). There was only rare use of other colloids; until 2012 few selected patients received small amounts of gelatine infusions. HES 10% was used only in rare cases after January 2011 and the use of HES 6% declined in 2013.

We hereby present a study on renal failure in patients with non-traumatic subarachnoid haemorrhage treated with hydroxyethyl starch. During the last decades clinically available and used intravenous fluids changed, therefore we compared different groups of patients with SAH treated with different regimens of intravenous fluid administration. In contrast to recently published studies in critically ill patients we could not demonstrate an association between HES application or its cumulative doses and renal dysfunction or the necessity to apply renal replacement therapy [6–8]. The incidence of acute kidney injury in our patients depended on the pre-existing renal dysfunction, but not on the HES application. It was reversible in most cases as indicated by the low frequency of renal replacement therapy. The higher duration of acute kidney injury in the crystalloid group when compared to the HES group might be explained by the higher rate of severe forms of acute kidney injury with KDIGO state 2 and 3 in the crystalloid group.

In summary, we could not demonstrate a statistically significant association between the application of HES and the incidence of acute kidney injury in patients with SAH. Additionally, as the incidence of vasospasm was higher in the HES group, our data suggest that omitting HES was not associated with harm in SAH patients. These results provide arguments that termination of the HES application in our SAH patients was justified. In the light of the retrospective character of the study results should be interpreted with caution.