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Effect of volume loading with 1 liter intravenous infusions of 0.9% saline, 4% succinylated gelatine (Gelofusine) and 6% hydroxyethyl starch (Voluven) on blood volume and endocrine responses: A randomized, three-way crossover study in healthy volunteers

Lobo, Dileep N. DM, FRCS; Stanga, Zeno MD; Aloysius, Mark M. MRCS; Wicks, Catherine BMedSci, BM, BS; Nunes, Quentin M. MRCS; Ingram, Katharine L. FRCA; Risch, Lorenz MD, MPH; Allison, Simon P. MD, FRCP

doi: 10.1097/CCM.0b013e3181bc80f1
Clinical Investigations

Objective: To study the changes in blood volume and hormones controlling sodium and water homeostasis after infusions of 0.9% saline, Gelofusine (4% succinylated gelatin in 0.7% saline, weight-average molecular weight 30 kD), and Voluven (6% hydroxyethyl starch in 0.9% saline, weight-average molecular weight 130 kD) in healthy volunteers.

Design: Randomized, three-way crossover study.

Setting: University teaching hospital.

Subjects: Ten healthy adult male volunteers.

Interventions: Volunteers received 1-L infusions of 0.9% saline, Gelofusine, and Voluven over 1 hr on three occasions. Body weight, hematocrit, serum biochemistry, and plasma concentrations of vasopressin, aldosterone, brain natriuretic peptide, and total renin were measured before infusion and hourly thereafter for 6 hrs. Changes in body water, blood volume, and extravascular fluid volume were calculated.

Measurements and Main Results: Although changes in body weight (total body water) after the infusions were similar, blood volume expansion by the two colloids was significantly greater than that produced by 0.9% saline (p < .01). At the end of infusions, 68%, 21%, and 16% of the infused volumes of 0.9% saline, Gelofusine, and Voluven, respectively, had escaped from the intravascular space to the extravascular space. Over the 6 hrs, the magnitude and duration of blood volume expansion by the two colloids were similar (p = .70). There were no significant differences in urinary volume, osmolality, and sodium content after the three infusions. Hormonal changes were similar after the three infusions, with the increase in natriuretic peptide being transient. The reduction in aldosterone and total renin concentrations was more sustained.

Conclusions: The effects of Gelofusine and Voluven were similar despite the 100 kD difference in weight-average molecular weight. Excretion of an acute fluid load containing sodium and chloride may be dependent on a sustained suppression of the renin-angiotensin-aldosterone system rather than on natriuretic peptides.

From the Division of Gastrointestinal Surgery (DNL, MMA, CW, QMN, SPA), Nottingham Digestive Diseases Centre NIHR Biomedical Research Unit, Nottingham University Hospitals, Queen's Medical Centre, Nottingham, UK; Divison of Endocrinology (ZS), Diabetes and Clinical Nutrition and Department of Internal Medicine, Inselspital, Berne, Switzerland; Department of Anaesthesia (KLI), Nottingham University Hospitals, Queen's Medical Centre, Nottingham, UK; and IRL Medical Laboratories (LR), Schaan, Liechtenstein.

This paper was presented, in part, to the International Conference of the Association of Surgeons of Great Britain and Ireland, Glasgow, May 2009, and at the International Surgical Week, Adelaide, September 2009. It has been published in abstract form [Br J Surg 2009; 96(S4):29 and World J Surg 2009; 33(S1):S10].

Supported, in part, by departmental funds from the School of Clinical Sciences, University of Nottingham, and the Division of Endocrinology, Diabetes and Clinical Nutrition, Inselspital, University of Bern, Switzerland.

Dr. Lobo has received honoraria from B Braun and Baxter Healthcare and Fresenius Kabi; Dr. Lobo has also received grant support from Fresenius Kabi for unrelated work. The remaining authors have not disclosed any potential conflicts of interest.

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© 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins