Isoproternenol increases vascular volume expansion and urinary output after a large crystalloid bolus in healthy volunteers.

Asmussen, Sven; Salter, Michael; Prough, Donald S; Kramer, George C; Svensen, Christer; Sheffield-Moore, Melinda; Kinsky, Michael P

BACKGROUND The primary goal of fluid therapy is to maintain fluid homeostasis. Commonly used isotonic crystalloids are only marginally effective and contribute to fluid excess syndrome. In patients with decreased cardiovascular reserve, fluid therapy alone is not sufficient to maintain end-organ perfusion. Therefore, inotropes or vasoactive drugs are used to supplement fluid infusion. Recent animal data suggest that coinfusion of adrenergic agents modulate the distribution of fluid between the vascular and extravascular/interstitial compartments after a fluid bolus. We sought to determine if this effect would translate in humans by coadministering a β-adrenergic agonist with fluid. METHODS Nine healthy volunteers (aged 21-50 years) were randomly paired and received either a continuous isoproterenol infusion (ISO: 0.05 μg/kg per minute) or 0.9% saline (control [CON]) 30min prior to a 25 mL/kg 0.9% NaCl fluid bolus. Hemodynamics, ventricular volume and function, and microcirculatory determinants (capillary filtration coefficient and oncotic pressure) were measured. Vascular and extravascular volume and fluid balance were determined. RESULTS Compared with CON, ISO significantly increased heart rate (CON: 64.2 ± 4.1 beats/min vs. ISO: 97.4 ± 5.7 beats/min) and cardiac output (CON: 4.4 ± 0.7 L/min vs. ISO: 10.2 ± 0.9) before fluid bolus. Isoproterenol significantly increased urinary output (ISO: 10.86 ± 1.95 vs. control: 6.53 ± 1.45 mL/kg) and reduced extravascular volume (7.98 ± 2.0 vs. 14.15 ± 1.1mL/kg). Isoproterenol prevented an increase in capillary filtration coefficient (1.74 ± 0.4 vs. 3.21 ± 0.4 mL/min per mmHg · 10). CONCLUSIONS Isoproterenol, a nonselective β-adrenergic agonist, augments vascular volume expansion and eliminates extravascular volume via enhanced diuresis, which may in part be due to enhanced endothelial barrier function.