Michael Salter

Release of neurotensin by selective perfusion of the jejunum with oleic acid in dogs

Plasma neurotensin concentrations are rapidly elevated after oral ingestion or intraduodenal infusion of fat, apparently before fat reaches the ileum where neurotensin is highly concentrated. The purpose of this study was to investigate the site of neurotensin release and to determine whether neurotensin is released by direct luminal stimulation by fat in conscious dogs. Dogs were prepared with isolated jejunal or ileal segments and portal vein catheters. Release of neurotensin into the portal venous blood was examined by selective perfusion of each intestinal segment with sodium oleáte. The results of this study show that selective perfusion of the jejunum, but not the ileum, with sodium oleate, caused a significant release of neurotensin. We speculate that release of ileal neurotensin is not due to direct luminal stimulation, but is mediated by local neural or humoral intermediates.

Trending, Accuracy, and Precision of Noninvasive Hemoglobin Monitoring During Human Hemorrhage and Fixed Crystalloid Bolus

ABSTRACT Automated critical care systems for en route care will rely heavily on noninvasive continuous monitoring. It has been reported that noninvasive assessment of blood hemoglobin via CO-oximetry (SpHb) assessed by spot measurements lacks sufficient accuracy for clinical decision making in trauma patients. However, the precision and utility of trending of continuous hemoglobin have not been evaluated in hemorrhaging humans. This study measured the trending and concordance of SpHb changes during dynamic variations resulting from controlled hemorrhage with concomitant fluid infusion. With institutional review board approval and informed consent, 12 healthy volunteers under general anesthesia were subjected to hemorrhage (10 mL/kg for 15 min) accompanied by Ringer’s lactate solution infusion (30 mL/kg for 20 min). The SpHb was measured continuously by the Masimo Radical-7, whereas total blood hemoglobin was measured by arterial blood sampling. Trend analysis, assessed by plots of SpHb against time of 12 subjects, shows consistent falls in SpHb during hemodilution without exception. Four-quadrant concordance analysis was 95.4% with an exclusion zone of 1 g/dL. Spot comparisons of 106 data pairs (SpHb and total blood hemoglobin) showed that 50% exhibited an error of more than 1 g/dL with bias of 1.08 ± 0.82 g/dL and 95% limits of agreement of -0.5 to 2.6. Both trend analysis and concordance analysis suggest high precision of pulse CO-oximetry during hemodilution by hemorrhage and fluid bolus in human volunteers. However, accuracy was similar to other studies and therefore the use of pulse CO-oximetry alone is likely insufficient to make transfusion decisions.

Vascular and extravascular volume expansion of dobutamine and norepinephrine in normovolemic sheep

In low-flow states, such as circulatory shock, both fluids and catecholamines are often coadministered. We have previously found that adrenergic agents alter volume expansion after a fluid bolus. The present study tested the volume expansion properties of dobutamine and norepinephrine in sheep treated with (series 1) and without (series 2) a fluid bolus. Series 1 (n = 6 per group): no drug (control), dobutamine (10 &mgr;g · kg−1 · min−1), or norepinephrine (1.0 &mgr;g · kg−1 · min−1) was begun 30 min before a 24-mL · kg−1, 20-min, 0.9% NaCl bolus. The effect of drug and fluid on plasma volume (&Dgr;PV), urinary output (UOP), and extravascular volume (&Dgr;EVV) was determined. Series 2: Identical protocol but no fluid bolus. Series 1: the fluid bolus resulted in a peak and sustained &Dgr;PV expansion. Norepinephrine (7.5 ± 0.9 mL · kg−1) and dobutamine (9.5 ± 1.1 mL · kg−1) significantly increased &Dgr;PV compared with control (3.8 ± 1.1 mL · kg−1). Cumulative UOP was reduced by dobutamine (3.8 ± 1.4 mL · kg−1) compared with norepinephrine (25.1 ± 3.9 mL · kg−1) and control (16.9 ± 4.0 mL · kg−1). Norepinephrine increased &Dgr;PV, while reducing &Dgr;EVV after bolus. Series 2: &Dgr;PV was unchanged in the control group. Dobutamine and norepinephrine increased &Dgr;PV over time, 5.1 ± 0.5 and 4.0 ± 0.5 mL · kg−1, respectively. At study end, UOP was lowest in dobutamine. Norepinephrine resulted in loss of &Dgr;EVV fluid. data suggest a novel role for adrenergic receptors in regulating vascular and EVV expansion. &bgr;-Adrenergic agonists enhance vascular volume expansion, whereas &agr;-adrenergic agonists eliminate extravascular fluid.

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

ABSTRACT 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 &bgr;-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 &mgr;g/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 · 10−3). Conclusions: Isoproterenol, a nonselective &bgr;-adrenergic agonist, augments vascular volume expansion and eliminates extravascular volume via enhanced diuresis, which may in part be due to enhanced endothelial barrier function.

Closed-loop Control of Fio2 Rapidly Identifies Need For Rescue Ventilation and Reduces Ards Severity in a Conscious Sheep Model of Burn and Smoke Inhalation Injury.

ABSTRACT Pulmonary injury can be characterized by an increased need for fraction of inspired oxygen or inspired oxygen percentage (FiO2) to maintain arterial blood saturation of oxygenation (SaO2). We tested a smart oxygenation system (SOS) that uses the activity of a closed-loop control FiO2 algorithm (CLC-FiO2) to rapidly assess acute respiratory distress syndrome (ARDS) severity so that rescue ventilation (RscVent) can be initiated earlier. After baseline data, a pulse-oximeter (noninvasive saturation of peripheral oxygenation [SpO2]) was placed. Sheep were then subjected to burn and smoke inhalation injury and followed for 48 h. Initially, sheep were spontaneously ventilating and then randomized to standard of care (SOC) (n = 6), in which RscVent began when partial pressure of oxygen (PaO2) < 90 mmHg or FiO2 < 0.6, versus SOS (n = 7), software that incorporates and displays SpO2, CLC-FiO2, and SpO2/CLC-FiO2 ratio, at which RscVent was initiated when ratio threshold < 250. RscVent was achieved using a G5 Hamilton ventilator (Bonaduz, Switzerland) with adaptive pressure ventilation and adaptive support ventilation modes for SOC and SOS, respectively. Outcomes: the time difference from when SpO2/FiO2 < 250 to RscVent initiation was 4.7 ± 0.6 h and 0.2 ± 0.1 h, SOC and SOS, respectively (P < 0.001). Oxygen responsiveness after RscVent, defined as SpO2/FiO2 > 250 occurred in 4/7, SOS and 0/7, SOC. At 48 h the SpO2/FiO2 ratio was 104 ± 5 in SOC versus 228 ± 59 in SOS (P = 0.036). Ventilatory compliance and peak airway pressures were significantly improved with SOS versus SOC (P < 0.001). Data suggest that SOS software, e.g. SpO2/CLC-FiO2 ratio, after experimental ARDS can provide a novel continuous index of pulmonary function that is apparent before other clinical symptoms. Earlier initiation of RscVent translates into improved oxygenation (reduces ARDS severity) and ventilation.

Effect of hemorrhage rate on early hemodynamic responses in conscious sheep

Physiological compensatory mechanisms can mask the extent of hemorrhage in conscious mammals, which can be further complicated by individual tolerance and variations in hemorrhage onset and duration. We assessed the effect of hemorrhage rate on tolerance and early physiologic responses to hemorrhage in conscious sheep. Eight Merino ewes (37.4 ± 1.1 kg) were subjected to fast (1.25 mL/kg/min) and slow (0.25 mL/kg/min) hemorrhages separated by at least 3 days. Blood was withdrawn until a drop in mean arterial pressure (MAP) of >30 mmHg and returned at the end of the experiment. Continuous monitoring included MAP, central venous pressure, pulmonary artery pressure, pulse oximetry, and tissue oximetry. Cardiac output by thermodilution and arterial blood samples were also measured. The effects of fast versus slow hemorrhage rates were compared for total volume of blood removed and stoppage time (when MAP < 30 mmHg of baseline) and physiological responses during and after the hemorrhage. Estimated blood volume removed when MAP dropped 30 mmHg was 27.0 ± 4.2% (mean ± standard error) in the slow and 27.3 ± 3.2% in the fast hemorrhage (P = 0.47, paired t test between rates). Pressure and tissue oximetry responses were similar between hemorrhage rates. Heart rate increased at earlier levels of blood loss during the fast hemorrhage, but hemorrhage rate was not a significant factor for individual hemorrhage tolerance or hemodynamic responses. In 5/16 hemorrhages MAP stopping criteria was reached with <25% of blood volume removed. This study presents the physiological responses leading up to a significant drop in blood pressure in a large conscious animal model and how they are altered by the rate of hemorrhage.

Optoacoustic measurement of central venous oxygenation for assessment of circulatory shock: clinical study in cardiac surgery patients

Circulatory shock is a dangerous medical condition, in which blood flow cannot provide the necessary amount of oxygen to organs and tissues. Currently, its diagnosis and therapy decisions are based on hemodynamic parameters (heart rate, blood pressure, blood gases) and mental status of a patient, which all have low specificity. Measurement of mixed or central venous blood oxygenation via catheters is more reliable, but highly invasive and associated with complications. Our previous studies in healthy volunteers demonstrated that optoacoustic systems provide non-invasive measurement of blood oxygenation in specific vessels, including central veins. Here we report our first results of a clinical study in coronary artery bypass graft (CABG) surgery patients. We used a medical-grade OPO-based optoacoustic system developed in our laboratory to measure in real time blood oxygenation in the internal jugular vein (IJV) of these patients. A clinical ultrasound imaging system (GE Vivid e) was used for IJV localization. Catheters were placed in the IJV as part of routine care and blood samples taken via the catheters were processed with a CO-oximeter. The optoacoustic oxygenation data were compared to the CO-oximeter readings. Good correlation between the noninvasive and invasive measurements was obtained. The results of these studies suggest that the optoacoustic system can provide accurate, noninvasive measurements of central venous oxygenation that can be used for patients with circulatory shock.

The C3PO project: a laser communication system concept for small satellites

The satellite market is shifting towards smaller (micro and nanosatellites), lowered mass and increased performance platforms. Nanosatellites and picosatellites have been used for a number of new, innovative and unique payloads and missions. This trend requires new concepts for a reduced size, a better performance/weight ratio and a reduction of onboard power consumption. In this context, disruptive technologies, such as laser-optical communication systems, are opening new possibilities. This paper presents the C3PO1 system, “advanced Concept for laser uplink/ downlink CommuniCation with sPace Objects”, and the first results of the development of its key technologies. This project targets the design of a communications system that uses a ground-based laser to illuminate a satellite, and a Modulating Retro-Reflector (MRR) to return a beam of light modulated by data to the ground. This enables a downlink, without a laser source on the satellite. This architecture suits well to small satellite applications so as high data rates are potentially provided with very low board mass. C3PO project aims to achieve data rates of 1Gbit/s between LEO satellites and Earth with a communication payload mass of less than 1kilogram. In this paper, results of the initial experiments and demonstration of the key technologies will be shown.

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.

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

ABSTRACT 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 &Dgr;mean ± 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 (&Dgr;E/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.