title: Dextran fractional clearance studies in acute dengue infection.
abstract: BACKGROUND
  Although increased capillary permeability is the major clinical feature associated with severe dengue infections the mechanisms underlying this phenomenon remain unclear. Dextran clearance methodology has been used to investigate the molecular sieving properties of the microvasculature in clinical situations associated with altered permeability, including during pregnancy and in various renal disorders. In order to better understand the characteristics of the vascular leak associated with dengue we undertook formal dextran clearance studies in Vietnamese dengue patients and healthy volunteers.
  
  
  RESULTS
  We carried out serial clearance studies in 15 young adult males with acute dengue and evidence of vascular leakage a) during the phase of maximal leakage and b) one and three months later, as well as in 16 healthy control subjects. Interestingly we found no difference in the clearance profiles of neutral dextran solutions among the dengue patients at any time-point or in comparison to the healthy volunteers.
  
  
  CONCLUSIONS
  The surface glycocalyx layer, a fibre-matrix of proteoglycans, glycosaminoglycans, and plasma proteins, forms a complex with the underlying endothelial cells to regulate plasma volume within circumscribed limits. It is likely that during dengue infections loss of plasma proteins from this layer alters the permeability characteristics of the complex; physical and/or electrostatic interactions between the dextran molecules and the glycocalyx structure may temporarily restore normal function, rendering the technique unsuitable for assessing permeability in these patients. The implications for resuscitation of patients with dengue shock syndrome (DSS) are potentially important. It is possible that continuous low-dose infusions of dextran may help to stabilize the permeability barrier in patients with profound or refractory shock, reducing the need for repeated boluses, limiting the total colloid volume required. Formal clinical studies should help to assess this strategy as an alternative to conventional fluid resuscitation for severe DSS.
authors: Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam. jpouplin@oucru.org
authors: Julie
authors: J
authors: Nguyen-Pouplin
authors: Thomas
authors: T
authors: Pouplin
authors: Toi Pham
authors: TP
authors: Van
authors: Trung Dinh
authors: TD
authors: The
authors: Dung Nguyen
authors: DN
authors: Thi
authors: Jeremy
authors: J
authors: Farrar
authors: Hien Tran
authors: HT
authors: Tinh
authors: Bridget
authors: B
authors: Wills
mesh_terms: D000328:Adult; D002196:Capillaries / Q000503:physiopathology*; D002199:Capillary Permeability; D003715:Dengue / Q000473:pathology*; D003911:Dextrans / Q000378:metabolism* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate
chemical_list: D003911:Dextrans