researchCapillary leakage in post-cardiac arrest survivors during therapeutic hypothermia-a prospective , randomised study

Background: Fluids are often given liberally after the return of spontaneous circulation. However, the optimal fluid regimen in survivors of cardiac arrest is unknown. Recent studies indicate an increased fluid requirement in postcardiac arrest patients. During hypothermia, animal studies report extravasation in several organs, including the brain. We investigated two fluid strategies to determine whether the choice of fluid would influence fluid requirements, capillary leakage and oedema formation. Methods: 19 survivors with witnessed cardiac arrest of primary cardiac origin were allocated to either 7.2% hypertonic saline with 6% poly (O-2-hydroxyethyl) starch solution (HH) or standard fluid therapy (Ringer's Acetate and saline 9 mg/ ml) (control). The patients were treated with the randomised fluid immediately after admission and continued for 24 hours of therapeutic hypothermia. Results: During the first 24 hours, the HH patients required significantly less i.v. fluid than the control patients (4750 ml versus 8010 ml, p = 0.019) with comparable use of vasopressors. Systemic vascular resistance was significantly reduced from 0 to 24 hours (p = 0.014), with no difference between the groups. Colloid osmotic pressure (COP) in serum and interstitial fluid (p < 0.001 and p = 0.014 respectively) decreased as a function of time in both groups, with a more pronounced reduction in interstitial COP in the crystalloid group. Magnetic resonance imaging of the brain did not reveal vasogenic oedema. Conclusions: Post-cardiac arrest patients have high fluid requirements during therapeutic hypothermia, probably due to increased extravasation. The use of HH reduced the fluid requirement significantly. However, the lack of brain oedema in both groups suggests no superior fluid regimen. Cardiac index was significantly improved in the group treated with crystalloids. Although we do not associate HH with the renal failures that developed, caution should be taken when using hypertonic starch solutions in these patients. Trial registration: NCT00347477. Background Few studies have described fluid requirements in cardiac arrest patients [1-3], but fluid infusion after ROSC is increasingly debated [4]. During hypothermia, animal studies report extravasation in several organs, including the brain [5,6]. Whether capillary leakage is present in man during therapeutic hypothermia, is not documented. This is of clinical interest, as oedema formation in a vulnerable OHCA-brain is considered harmful. Furthermore, this is underlined by the similarity between postresuscitation syndrome and sepsis [7,8]. Septic patients are known to have high fluid requirements, and outcome is improved by goal-directed fluid therapy [9]. Encouraged by the low cardiac output after cardiac arrest [1], fluid load would appear to be worth attempting. In addition, the induction of hypothermia by large volumes of cold intravenous infusions has gained in popularity [10]. * Correspondence: baard.heradstveit@helse-bergen.no 1 Department of Anaesthesia and Intensive Care, Haukeland University Hospital, Bergen, Norway Full list of author information is available at the end of the article © 2010 Heradstveit et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Heradstveit et al. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 2010, 18:29 http://www.sjtrem. com/content/18/1/29 Page 2 of 9 The application of a hypertonic colloid during cardiopulmonary bypass has been shown to reduce fluid overload [11,12]. Colloids tend to cause less tissue oedema than crystalloids [13] and, as regards inflammatoryrelated leakages, hydroxyethyl starch could have an 'occlusive' effect on damaged capillaries, subsequently limiting extravasation [14]. Furthermore, hypertonic solutions recruit fluid from the intracellular space to the capillaries, and, during CPR in an animal model, these solutions increased myocardial blood flow and the survival rate [15]. The aim of the study was to determine whether a capillary leakage was present in OHCA survivors during therapeutic hypothermia. We compared two fluid regimens and studied the impact on capillary leakage. The intervention group received an additional 500 ml of 7.2% hypertonic saline with 6% poly (O-2-hydroxyethyl) starch solution during the first 24 hours, and was compared with standard therapy. The primary endpoint was the amount of fluid administered during the first 24 hours. The secondary endpoint was the magnitude of capillary leakage as a surrogate marker for oedema formation. Methods Ethics The study was approved by the Regional Committees for Medical Research Ethics, the Data Inspectorate, the Directorate for Health and Social Affairs and the Norwegian Medicines Agency. Deferred consent was used, and the patients' families were entitled to withdraw the patients at any time. All patients included were informed about the study when they were able to receive the information and signed a written informed consent form. Study population and environment The study was performed on 19 patients with witnessed out-of-hospital cardiac arrest (OHCA) and carried out between September 2005 and March 2007 at Haukeland University Hospital (Bergen, Norway), an 1,100-bed hospital serving 600,000 people. All inclusion/exclusion criteria are presented in Table 1. The fluid intervention was initiated immediately after admission to the emergency room and continued for the first 24 hours. Treatment protocol On admission, the patients were allocated by means of stratified randomisation to one of two fluid regimens administered via infusion pumps: Ringer's Acetate and saline 9 mg/ml (control), or hypertonic colloid,7.2% NaCl with 6% Hydroxyethyl starch 200/0.5 (HyperHAES® Fresenius Kabi, Germany) (HH). Fluid was administered to achieve the treatment goals listed in Table 2. HH was limited to 500 ml per 24 hours (20 ml/hr). Further needs for fluid in the HH group were met by Ringer's Acetate/ saline 9 mg/ml. The control group received Ringer's Acetate and saline 9 mg/ml by turn during the observation period, in accordance with the standard treatment in the medical intensive care unit (MICU). Coronary intervention Patients with ST elevation, a new left bundle branch block or cardiogenic shock were referred immediately for coronary angiography and subsequent percutaneous coronary intervention (PCI). Magnetic resonance imaging Before admission to the MICU, after cardiac intervention and if the patient did not have an intra-aortic-balloon pump (IABP), magnetic resonance imaging (MRI) of the brain was planned (1.5 Tesla, conventional morphological and diffusion sequences). Repeated MRI was scheduled after 24 and 96 hours. Intensive care treatment and monitoring Cardiac arrest data were recorded according to the Utstein style [16]. In the MICU, monitoring was perTable 1: Criteria for inclusion. Inclusion criteria Exclusion criteria • Witnessed cardiac arrest with a probable cardiac cause. (Ventricular fibrillation, tachycardia, asystole and pulseless electrical activity) • Terminal illness,