Closed-Loop- and Decision-Assist-Guided Fluid Therapy of Human Hemorrhage.

OBJECTIVES: We sought to evaluate the efficacy, efficiency, and physiologic consequences of automated, endpoint-directed resuscitation systems and compare them to formula-based bolus resuscitation. DESIGN: Experimental human hemorrhage and resuscitation. SETTING: Clinical research laboratory. SUBJECTS: Healthy volunteers. INTERVENTIONS: Subjects (n = 7) were subjected to hemorrhage and underwent a randomized fluid resuscitation scheme on separate visits 1) formula-based bolus resuscitation; 2) semiautonomous (decision assist) fluid administration; and 3) fully autonomous (closed loop) resuscitation. Hemodynamic variables, volume shifts, fluid balance, and cardiac function were monitored during hemorrhage and resuscitation. Treatment modalities were compared based on resuscitation efficacy and efficiency. MEASUREMENTS AND MAIN RESULTS: All approaches achieved target blood pressure by 60 minutes. Following hemorrhage, the total amount of infused fluid (bolus resuscitation: 30 mL/kg, decision assist: 5.6 ± 3 mL/kg, closed loop: 4.2 ± 2 mL/kg; p < 0.001), plasma volume, extravascular volume (bolus resuscitation: 17 ± 4 mL/kg, decision assist: 3 ± 1 mL/kg, closed loop: -0.3 ± 0.3 mL/kg; p < 0.001), body weight, and urinary output remained stable under decision assist and closed loop and were significantly increased under bolus resuscitation. Mean arterial pressure initially decreased further under bolus resuscitation (-10 mm Hg; p < 0.001) and was lower under bolus resuscitation than closed loop at 20 minutes (bolus resuscitation: 57 ± 2 mm Hg, closed loop: 69 ± 4 mm Hg; p = 0.036). Colloid osmotic pressure (bolus resuscitation: 19.3 ± 2 mm Hg, decision assist, closed loop: 24 ± 0.4 mm Hg; p < 0.05) and hemoglobin concentration were significantly decreased after bolus fluid administration. CONCLUSIONS: We define efficacy of decision-assist and closed-loop resuscitation in human hemorrhage. In comparison with formula-based bolus resuscitation, both semiautonomous and autonomous approaches were more efficient in goal-directed resuscitation of hemorrhage. They provide favorable conditions for the avoidance of over-resuscitation and its adverse clinical sequelae. Decision-assist and closed-loop resuscitation algorithms are promising technological solutions for constrained environments and areas of limited resources.

The physiologic responses to a fluid bolus administration in old and young healthy adults.

BACKGROUND: Organ function is known to decline with age. Optimizing cardiac, pulmonary and renal function in older adults has led to significant improvements in perioperative care. However, when substantial blood loss and fluid shifts occur, perioperative outcomes still remains poor, especially in older adults. We suspect that this could be due to age-related changes in endothelial function-an organ controlling the transport of fluid and solutes. The capillary filtration coefficient (CFC) is an important determinant of fluid transport. The CFC can be measured in vivo, which provides a tool to estimate endothelial barrier function. We have previously shown that the CFC increases when giving a fluid bolus resulting in increased vascular and extravascular volume expansion, in young adults. This study aimed to compare the physiologic determinants of fluid distribution in young versus older adults so that clinicians can best optimize perioperative fluid therapy. METHODS: Ten healthy young volunteers (ages 21-35) and nine healthy older volunteers (ages 60-75) received a 10 mL/kg fluid bolus over the course of twenty minutes. Hemodynamics, systolic and diastolic heart function, fluid volumetrics and microcirculatory determinants were measured before, during, and after the fluid bolus. RESULTS: Diastolic function was reduced in older versus younger adults before and after fluid bolus (P < 0.01). Basal CFC and plasma oncotic pressure were lower in the older versus younger adults. Further, CFC did not increase in older adults following the fluid bolus, whereas it did in younger adults (p < 0.05). Cumulative urinary output, while lower in older adults, was not significantly different (p = 0.059). Mean arterial pressure and systemic vascular resistance were elevated in the older versus younger adults (p < 0.05). CONCLUSION: Older adults show a less reactive CFC to a fluid bolus, which could reduce blood to tissue transport of fluid. Diastolic dysfunction likely contributes to fluid maldistribution in older adults.

Intrathoracic Pressure Regulation Augments Stroke Volume and Ventricular Function in Human Hemorrhage.

Obtaining intravenous (i.v.) access for fluid administration is a critical step in treating hemorrhage. However, expertise, supplies, and personnel to accomplish this task can be delayed or even absent in austere environments. An alternative approach that can "buy time" and improve circulation when i.v. fluids are absent is needed. Preclinical studies show that intrathoracic pressure regulation (ITPR) can increase perfusion in hypovolemia in the absence of i.v. fluid. We compared ITPR with placebo in humans undergoing a 15% hemorrhage under general anesthesia. Paired healthy volunteers (n = 7, aged 21 - 35 years) received either ITPR or placebo on different study days. Institutional review board informed consent was obtained. Subjects were anesthetized using propofol, intubated, and mechanically ventilated and hemorrhaged (10 mL/kg). Twenty minutes after hemorrhage, ITPR (-12 cm H2O vacuum) or placebo (device but no vacuum) was administered for another 60 min. Intravenous fluid was administered when systolic blood pressure was less than 85 mmHg. Hemodynamics, cardiac function by echocardiography, and volumetric data were compared. Data were expressed in Δmean ± SEM before and after ITPR/placebo intervention. There were no differences in mean arterial pressure (ITPR, 2.1 ± 3 mmHg; placebo, -0.7 ± 3 mmHg) or fluid infused (ITPR, 17.4 ± 4 mL/kg; placebo, 18.6 ± 5 mL/kg). Urinary output and plasma volume also were not significantly different. Intrathoracic pressure regulation augmented stroke volume (ITPR, 22 ± 5 mL, placebo, 6 ± 4 mL; P < 0.05), ejection fraction (ITPR, 4% ± 1%; placebo, 0% ± 1%), and diastolic function (ΔE/e') (ITPR, -0.8 ± 0.4 vs. placebo, +0.81 ± 0.6; P < 0.05). Intrathoracic pressure regulation did not improve mean arterial pressure in healthy volunteers aged 21 to 35 years. However, ITPR augmented stroke volume, which could be caused by improved ventricular function.