Effect of esmolol on fluid therapy in normovolemia and hypovolemia.

beta-Adrenergic agonists can enhance vascular volume expansion after a fluid bolus. The present study addresses how the beta-adrenergic antagonist esmolol influences volume expansion and fluid balance during normovolemia (series 1) and hypovolemia (series 2). Sheep were instrumented, and the spleen was removed. For series 1, continuous infusion of 50 to 100 microg.kg(-1).min(-1) esmolol (n = 6) or control (no drug; n = 6) was begun 30 min before administration of a 24-mL kg(-1) 20-min bolus of 0.9% NaCl. For series 2, anesthetized sheep were infused with 50 to 100 microg.kg(-1).min(-1) esmolol (n = 6) or control (no drug; n = 6) 30 min before a-20 mL kg(-1) hemorrhage. Fluid resuscitation (0.9% NaCl) was begun 30 min after hemorrhage. The 24-mL kg(-1) 20-min bolus was followed by titrated fluid therapy. Hemoglobin, fluid in, and urinary output were used to calculate changes in plasma volume (DeltaPV), extravascular volume (DeltaEVV = fluid in - urinary output - DeltaPV), volume expansion efficiency (VEE = fluid in / DeltaPV), and fluid distribution ratio (DeltaPV/DeltaEVV). Hemodynamics for both series were similar with the exception of heart rate. In series 1, peak DeltaPV was 9.1 +/- 1.0 mL kg(-1) in control and 3.7 +/- 1.0 mL kg(-1) at study end. Esmolol resulted in a lower peak DeltaPV (6.4 +/- 2.0 mL kg(-1)) and a negative DeltaPV (-0.4 +/- 0.6 mL kg(-1)) at study's end. Urinary output was lower, and EVV was greater with esmolol. In series 2, esmolol increased fluid requirements (67 +/- 7 mL kg(-1)) compared with control (54 +/- 5 mL kg(-1)). Esmolol reduced DeltaPV/DeltaEVV. These data suggest that esmolol impairs the vascular retention of fluid and may increase the amount of volume support during fluid resuscitation.

Hypertonic 15% sodium pyruvate offers no initial resuscitation advantage compared with 8% hypertonic NACl in sheep with multiple hemorrhages.

Initial fluid resuscitation of hemorrhagic shock might be enhanced by the infusion of monocarboxylate-energy substrates. We evaluated hemodynamics, metabolism, and fluid dynamics for initial resuscitation of hemorrhage using small volume 15% sodium pyruvate solution (HPY) compared with osmotically matched 8% hypertonic saline (HS). Instrumented conscious sheep were hemorrhaged 25 mL/kg at time zero through 15 min (T0-T15) and 5 mL/kg for 5 min at T50 to T55 and T70 to T75. Fluid resuscitation from T30 to T180 was performed by a computer-controlled closed-loop system, which titrated infusion rate to a mean arterial pressure of 90 mmHg. Initial infusion was 4 mL/kg of either HPY or HS, followed by the administration of lactated Ringer. Both HPY and HS restored cardiac index similarly. The lactate/pyruvate ratio was used to assess metabolic debt and was significantly higher (T180), whereas oxygen delivery was significantly lower (T120) with HPY versus HS. Total fluid administered was similar, with 43.7 +/- 6.2 mL/kg for HPY and 39.4 +/- 6.8 mL/kg for HS. Plasma volume was similarly increased and approached baseline values for both groups. Initial resuscitation with small volume HPY offered no hemodynamic or metabolic advantage compared with small volume HS when the fluids were infused to an end point pressure.

Enteral resuscitation of burn shock using World Health Organization oral rehydration solution: a potential solution for mass casualty care.

Enteral resuscitation could provide a means to resuscitate burn shock when intravenous (IV) therapy is unavailable, such as in mass disasters. We evaluated the extent of intestinal absorption and resuscitative effects of World Health Organization Oral Rehydration Solution after a 40% TBSA burn in anesthetized swine compared with the IV infusion of lactated Ringer's infused by Parkland formula. Plasma volume (PV) was measured using indocyanine green dye dilution. Intestinal absorption was assessed using phenol red as a nonabsorbable marker. Changes in hematocrit, hemodynamics, and measured PV showed equivalent resuscitative effects of enteral and IV resuscitation. The duodenal fluid absorption rate started at 77 +/- 32 ml/hr per meter of intestine during the first hour and increased to 296 +/- 40 ml/hr during the fourth hour of resuscitation, with a total of 93 +/- 2% of World Health Organization Oral Rehydration Solution infused into the intestine being absorbed. Intestinal absorption rates after burn injury are sufficient to resuscitate a 40% TBSA burn.

Normotensive and hypotensive closed-loop resuscitation using 3.0% NaCl to treat multiple hemorrhages in sheep.

OBJECTIVE: NaCl solutions (7.5%) have been reported to be effective for resuscitation in animals and trauma patients, but these solutions are not approved for use in the United States. We hypothesized that infusion of Food and Drug Administration-approved 3% NaCl provides superior cardiovascular and metabolic function while reducing the overall fluid requirement for resuscitation of hemorrhage. Our objective was to compare four groups, hypotensive and normotensive resuscitation of hemorrhage using 3% NaCl (HS) or lactated Ringer's (LR). DESIGN: Sheep were hemorrhaged in three separate bleeds, 25 mL/kg at T0 mins and 5 mL/kg at both T50 and T70 mins. SETTING: University laboratory. SUBJECTS: Instrumented conscious sheep. INTERVENTIONS: Resuscitation was started at T30 mins and continued until T180. Normotensive and hypotensive resuscitation to mean arterial pressures of 90 mm Hg and 65 mm Hg, respectively, was performed with LR or HS using a closed-loop resuscitation system. MEASUREMENTS AND MAIN RESULTS: All four groups were successfully resuscitated to near target levels. Two animals in the hypotensive treatment protocols died during the second and third bleeding, one with the LR65 group and one with the HS65 group. Mean infused volumes were 59.9 +/- 7.0 and 18.0 +/- 5.9 in the LR90 and LR65 groups, respectively, and were 19.6 +/- 2.2 mL/kg and 13.3 +/- 5.7 mL/kg in the HS90 and HS65 treatments (p < .05; LR90 vs. each of the groups). Cardiac indexes were significantly higher with normotensive vs. hypotensive treatment. However, there was no hemodynamic advantage apparent with HS vs. LR when compared with the normotensive or hypotensive treatments. Some animals had high lactate levels (>10 mmol) with both of the hypotensive treatments and also with the HS90 treatment, while not one of the 11 LR90 treatment animals had lactate levels >8 mmol. CONCLUSIONS: Volume sparing was apparent with HS, but no hemodynamic or metabolic advantage was apparent when used for either normotensive or hypotensive resuscitation. Trends toward lower base excess values and higher occurrences of deaths only in the hypotensive treatment protocols suggest that resuscitation to a target mean arterial pressure of 65 mm Hg may be too low.