Study Compares Intensive Care Fluids Saline and Starch

SYDNEY, Oct. 17, 2012 /PRNewswire/ -- A landmark study by Australian and New Zealand researchers has found that a widely used starch fluid for resuscitation of patients in intensive care units (ICUs) provides no clinical benefit and its use results in increased acute kidney failure (haemodialysis) when compared to normal saline.

The findings of CHEST (The Crystalloid vs Hydroxyethyl Starch Trial) have the potential to change the way patients are treated in ICUs across the world.

Crystalloids and colloids are types of fluids used for resuscitation of acutely ill patients. Saline is the most commonly used and cheapest crystalloid solution. The more expensive starch is the most commonly used colloid solution globally. Despite widespread use internationally, starch was only licensed for use for the first time in Australia in 2006 and its use has increased since 2008.

Over the last three years, researchers from the Australian and New Zealand Intensive Care Society Clinical Trials Group and The George Institute for Global Health in Sydney have conducted the study to determine the efficacy and safety of starch solutions.

This large-scale, randomised-controlled trial was conducted in 32 hospitals in Australia and New Zealand. It was designed in a pragmatic way to represent current day practice, so that the results can be applied across Australia and New Zealand and worldwide.

Professor John Myburgh, Director of Critical Care and Trauma at The George Institute, said the primary question of the study was to determine whether starch increased the risk of dying in intensive care patients compared to saline. It additionally assessed whether currently used starch solutions, such as the one used in this study, increased the risk of kidney injury in ICU patients.

"The study tested 7000 adults treated in ICU, with half receiving either starch or saline for fluid resuscitation during their admission to the ICU," he said.

"Our results showed that in ICU patients, there was no significant difference in the risk of dying within three months between starch and saline.

"However, resuscitation with starch resulted in an increased number of patients being treated for kidney failure, primarily the use of acute renal replacement therapy (haemodialysis).

"There was a 21 percent higher incidence of use of renal replacement therapy in patients receiving starch compared to those given saline.

"The use of starch was also associated with a significant increase in side effects, particularly itching and skin rashes.

"The study does not provide evidence that resuscitation with starch compared to saline in intensive care provides any clinical benefit to the patient. We believe that these results substantiate the need for more detailed health economic analysis to give us a greater understanding of the cost to the patient and to the community of the use of starch. Our next phase of work will be to follow-up with our patients at six months to determine quality of life and long term effects.

"What our study demonstrates is that the selection of resuscitation fluid in critically ill patients requires careful consideration of its safety, its potential impact on patient-centred outcomes and its cost. This study substantially adds to the expanding body of high-quality data that will inform clinicians and public health about one of the most ubiquitous interventions in clinical medicine," Professor Myburgh said.

Full details of the CHEST study and results were published in the New England Journal of Medicine today.

Study oversight
The Crystalloid vs. Hydroxyethyl starch trial (CHEST) was an investigator-initiated, multicenter, prospective, blinded, parallel group, randomized-controlled trial conducted in 32 hospitals in Australia and New Zealand. The trial evaluated the safety and efficacy of 6% HES (130/0.4) in 0.9% saline when compared to 0.9% saline alone for fluid resuscitation in a heterogeneous population of adult patients treated in the ICU. The study management committee designed the study. The study protocol was endorsed by the Australian and New Zealand Intensive Care Society Clinical Trials Group. The study protocol was approved by a human research ethics committee of the Northern Sydney and Central Coast Area Health Service, the University of Sydney and by each participating institution. Written informed consent before randomization, or delayed consent was obtained from each patient, legal surrogate or institutional ethics committee. The study protocol and statistical analysis plan were published prior to unblinding treatment assignment. Statistical analyses were conducted at the George Institute for Global Health. The writing committee vouches for the data and statistical analyses, wrote the paper, decided to publish the paper and take responsibility for the final paper. The study was funded by a project grant from the National Health and Medical Research Council of Australia and by unrestricted grants from the New South Wales Ministry of Health and Fresenius Kabi (Bad Homburg, Germany). Fresenius Kabi supplied the study fluids and distributed them to participating sites. Funding agencies had no input into the design, conduct, data collection, statistical analysis or writing of the manuscripts. Independent analysis of the concentration and degree of molar substitution of HES and the concentration of saline was obtained for a random sample of 20 bags using gravimetric and nuclear magnetic resonance spectroscopic methods (Chemical Analysis Pty Ltd, Bulleen, Australia).

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Maya Kay,
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mkay@georgeinstitute.org.au

The George Institute for Global Health was ranked #1 research institution in the world for scientific impact by the SCImago Institution Rankings (SIR) World Report 2011, as an internationally-recognised health research organisation, undertaking high impact research focused specifically on the prevention and management of chronic diseases and injuries. Affiliated with the University of Sydney in Australia, Peking University Health Science Center in China, the University of Hyderabad in India and the University of Oxford in the United Kingdom, the Institute is a leader in the conduct of clinical, population health and health systems research. The Institute has a global network of medical experts working in a range of research fields as well as expertise in research design, project management, data management and statistical analysis. With a respected voice among global policy makers, The Institute has attracted significant funding support from governments, philanthropic organisations and corporations. George Institute research is regularly published in the top tier of academic journals internationally.