title: Timing of fluid resuscitation shapes the hemodynamic response to uncontrolled hemorrhage: analysis using dynamic modeling.
abstract: BACKGROUND
  Timing of fluid resuscitation with respect to intrinsic hemostasis is an unexplored aspect of uncontrolled hemorrhage, because most animal models do not allow direct monitoring of blood loss. The aim of this study was to define how timing of crystalloid administration affects the bleeding patient's hemodynamic response to fluids, using a computer model of blood volume changes during uncontrolled hemorrhage.
  
  
  METHODS
  A multi-compartment lumped-parameter deterministic model of intravascular volume changes in a bleeding adult patient was developed and implemented. The model incorporates empirical mathematical descriptions of intrinsic hemostasis and rebleeding.
  
  
  RESULTS
  The predicted hemodynamic response to uncontrolled hemorrhage closely corresponds to that seen in animal studies. A 2-L crystalloid bolus given during ongoing hemorrhage increases blood loss by 4 to 29%, an effect that is inversely related to the initial bleeding rate. A similar bolus given after intrinsic hemostasis may trigger rebleeding if given when the hemostatic clot is mechanically vulnerable. This period of clot vulnerability (ranging from 0-34 minutes) changes with both the initial bleeding rate and the rate of fluid administration.
  
  
  CONCLUSIONS
  The timing of crystalloid administration with respect to intrinsic hemostasis shapes the bleeding patient's hemodynamic response. An early bolus delays hemostasis and increases blood loss, while a late bolus may trigger rebleeding. These observations provide valuable insight into the hemodynamic response to fluid resuscitation.
authors.affiliation: Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Asher
authors.initials: A
authors.lastname: Hirshberg
authors.forename: David B
authors.initials: DB
authors.lastname: Hoyt
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Mattox
mesh_terms: D000328:Adult; D003198:Computer Simulation; D000077324:Crystalloid Solutions; D005440:Fluid Therapy / Q000379:methods*; D006439:Hemodynamics; D006801:Humans; D007552:Isotonic Solutions / Q000008:administration & dosage*; D008955:Models, Cardiovascular; D012771:Shock, Hemorrhagic / Q000503:physiopathology* / Q000628:therapy*; D013997:Time Factors
chemical_list: D000077324:Crystalloid Solutions; D007552:Isotonic Solutions