title: Dose response effects of hypertonic saline and dextran on cardiovascular responses and plasma volume expansion in sheep.
abstract: Despite the established efficacy of 7.5% NaCl/6% dextran-70 in the treatment of hypovolemia, the optimal formulation of a hyperosmotic/hyperoncotic small volume resuscitation solution has yet to be defined. The present study investigates the cardiovascular effects of hypertonic saline ranging from 3.75%-25% NaCl (HS) and dextran-70 (D-70) ranging from 3 to 24%. HS and D-70 were studied alone or in specific combinations at a dose of 4 mL/kg, in euvolemic sheep. Blood samples were collected before, during and up to 60 min after infusion of the test solutions. Dose-dependent effects of HS were immediate increases in cardiac output (CO) of 30-85%, falling to 10-35% over baseline after 60 min. HS concentrations over 3.75% significantly reduced systemic vascular resistance, but HS had no significant effect on mean arterial pressure (MAP). Plasma volume (PV) expansion with HS was an immediate, but transient increase of 12-35%. Infusion of D-70 induced sustained 10-20% increases in CO and 10-30% increases in PV, peaking 10 min post-infusion. D-70 also resulted in small (5-12 mmHg) increases in MAP. Cardiovascular effects of D-70 correlated with a dose-dependent increase in plasma dextran concentrations. All HS solutions significantly increased plasma Na, which peaked at > or = 200 mEq/L in the 25% group. The effects of D-70 and HS combined were additive on PV expansion and CO. These data indicate that concentrations of HS and D-70 which are higher than those currently used have a greater capability for expanding PV, but use of HS > 7.5% may be limited by resulting hypernatremia.
authors.affiliation: Division of Military Trauma Research, Letterman Army Institute of Research, Presidio of San Francisco, California 94129-6800, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Dubick
authors.forename: J M
authors.initials: JM
authors.lastname: Davis
authors.forename: T
authors.initials: T
authors.lastname: Myers
authors.forename: C E
authors.initials: CE
authors.lastname: Wade
authors.forename: G C
authors.initials: GC
authors.lastname: Kramer
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002302:Cardiac Output / Q000187:drug effects*; D003911:Dextrans / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004573:Electrolytes / Q000097:blood*; D005260:Female; D006982:Hypertonic Solutions / Q000494:pharmacology*; D010953:Plasma Volume / Q000187:drug effects / Q000502:physiology*; D012462:Saline Solution, Hypertonic / Q000494:pharmacology*; D012756:Sheep; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects*
chemical_list: D003911:Dextrans; D004573:Electrolytes; D006982:Hypertonic Solutions; D012462:Saline Solution, Hypertonic