Marko Sallisalmi1, Jyrki Tenhunen2, Anne Kultti3, Markku Tammi3, Ville Pettilä4. 1. Department of Surgery, Intensive Care Units, Division of Anaesthesia and Intensive Care Medicine, Helsinki University Hospital, Helsinki, Finland. 2. Critical Care Medicine Research Group, Department of Intensive Care Medicine, Tampere University Hospital, Tampere, Finland Department of Surgical Sciences, Anaesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden. 3. Institute of Biomedicine, University of Eastern Finland, Anatomy, Kuopio, Finland. 4. Department of Surgery, Intensive Care Units, Division of Anaesthesia and Intensive Care Medicine, Helsinki University Hospital, Helsinki, Finland University of Helsinki, Helsinki, Finland.
Abstract
BACKGROUND: Total plasma hyaluronan concentration is increased in septic shock. High-molecular-weight hyaluronan has a high intrinsic viscosity. Excessive release of high-molecular-weight hyaluronan in sepsis may induce hyperviscosity. METHODS: Plasma viscosity and the molecular size of plasma hyaluronan were determined in 20 patients with septic shock and in 20 healthy controls. Ex vivo, the effects of 0.4% and 0.047% high-molecular-weight hyaluronan 1560 kDa, 0.9% saline, and 6% hydroxy-ethyl-starch 130 kDa were compared to plasma and whole blood viscosity and red blood cell aggregation at a systemic hematocrit of 0.4, and at a microcirculatory hematocrit of 0.2. RESULTS: Plasma viscosity and total plasma protein content were low in septic shock patients on days one and four of treatment. Hyaluronan concentration was 10-fold higher in sepsis on day 1. Molecular weight of hyaluronan was relatively low, mostly 50-500 kDa, and did not change significantly in sepsis. Ex vivo, 0.4% high-molecular-weight hyaluronan 1560 kDa increased blood viscosity but did not promote red blood cell aggregation. Dilutions of 6% hydroxyl-ethyl-starch 130 kDa and 0.047% high-molecular-weight hyaluronan 1560 kDa had comparable effects on blood viscosity and red blood cell aggregation. CONCLUSIONS: Plasma viscosity of the septic patients remained low for four days despite markedly elevated concentration of relatively small-molecular-weight hyaluronan.
BACKGROUND: Total plasma hyaluronan concentration is increased in septic shock. High-molecular-weight hyaluronan has a high intrinsic viscosity. Excessive release of high-molecular-weight hyaluronan in sepsis may induce hyperviscosity. METHODS: Plasma viscosity and the molecular size of plasma hyaluronan were determined in 20 patients with septic shock and in 20 healthy controls. Ex vivo, the effects of 0.4% and 0.047% high-molecular-weight hyaluronan 1560 kDa, 0.9% saline, and 6% hydroxy-ethyl-starch 130 kDa were compared to plasma and whole blood viscosity and red blood cell aggregation at a systemic hematocrit of 0.4, and at a microcirculatory hematocrit of 0.2. RESULTS: Plasma viscosity and total plasma protein content were low in septic shockpatients on days one and four of treatment. Hyaluronan concentration was 10-fold higher in sepsis on day 1. Molecular weight of hyaluronan was relatively low, mostly 50-500 kDa, and did not change significantly in sepsis. Ex vivo, 0.4% high-molecular-weight hyaluronan 1560 kDa increased blood viscosity but did not promote red blood cell aggregation. Dilutions of 6% hydroxyl-ethyl-starch 130 kDa and 0.047% high-molecular-weight hyaluronan 1560 kDa had comparable effects on blood viscosity and red blood cell aggregation. CONCLUSIONS: Plasma viscosity of the septic patients remained low for four days despite markedly elevated concentration of relatively small-molecular-weight hyaluronan.
Authors: Christian Radke; Dagmar Horn; Christian Lanckohr; Björn Ellger; Michaela Meyer; Thomas Eissing; Georg Hempel Journal: Clin Pharmacokinet Date: 2017-07 Impact factor: 6.447