Nicole Ribeiro Marques

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.

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 Blood was withdrawn until a drop in mean arterial pressure (MAP) of 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.

Passive leg raising during pregnancy.

OBJECTIVE To determine if passive leg raising (PLR) significantly increases cardiac output in a cohort of healthy pregnant women during the third trimester. STUDY DESIGN Using a noninvasive monitor, baseline hemodynamic measurements for arterial blood pressure, systolic and diastolic blood pressure, heart rate, cardiac output, cardiac index, stroke volume, and systemic vascular resistances were obtained with patients in the semirecumbent position. Measurements were repeated after a 3-minute PLR maneuver in supine, right lateral decubitus, and left lateral decubitus positions. RESULTS After 10 minutes of bed rest, the cohorts mean baseline heart rate was 80 ± 12 beats/minute. Baseline stroke volume was 98 ± 14 mL, mean cardiac output was 7.8 ± 1.2 L/min, and mean cardiac index was 4.32 ± 0.63 L/min. The baseline systemic vascular resistance value was 893 ± 160 dynes/sec/cm(5). Baseline mean arterial blood pressure was 84 ± 11 mm Hg. Following a PLR maneuver in the supine position, heart rate decreased significantly. No difference was noted in other measurements. Findings were similar with PLR in the left lateral decubitus. PLR in the right lateral decubitus resulted in significantly decreased heart rate, cardiac output, and cardiac index. CONCLUSIONS PLR did not result in cardiac output recruitment in a cohort of healthy pregnant women during the third trimester.

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.

Long-term effect of critical illness after severe paediatric burn injury on cardiac function in adolescent survivors: an observational study

Background Sepsis, trauma, and burn injury acutely depress systolic and diastolic cardiac function; data on long-term cardiac sequelae of pediatric critical illness are sparse. This study evaluated long-term systolic and diastolic function, myocardial fibrosis, and exercise tolerance in survivors of severe pediatric burn injury. Methods Subjects at least 5 years after severe burn (post-burn:PB) and age-matched healthy controls (HC) underwent echocardiography to quantify systolic function (ejection fraction[EF%]), diastolic function (E/e′), and myocardial fibrosis (calibrated integrated backscatter) of the left ventricle. Exercise tolerance was quantified by oxygen consumption (VO2) and heart rate at rest and peak exercise. Demographic information, clinical data, and biomarker expression were used to predict long-term cardiac dysfunction and fibrosis. Findings Sixty-five subjects (PB:40;HC:25) were evaluated. At study date, PB subjects were 19±5 years, were at 12±4 years postburn, and had burns over 59±19% of total body surface area, sustained at 8±5 years of age. The PB group had lower EF% (PB:52±9%;HC:61±6%; p=0.004), E/e′ (PB:9.8±2.9;HC: 5.4±0.9;p<0.0001), VO2peak (PB:37.9±12;HC: 46±8.32 ml/min/kg; p=0.029), and peak heart rate (PB:161±26;HC:182±13bpm;p=0.007). The PB group had moderate (28%) or severe (15%) systolic dysfunction, moderate (50%) or severe diastolic dysfunction (21%), and myocardial fibrosis (18%). Biomarkers and clinical parameters predicted myocardial fibrosis, systolic dysfunction, and diastolic dysfunction. Interpretation Severe pediatric burn injury may have lasting impact on cardiac function into young adulthood and is associated with myocardial fibrosis and reduced exercise tolerance. Given the strong predictive value of systolic and diastolic dysfunction, these patients might be at increased risk for early heart failure, associated morbidity, and mortality. Funding Conflicts of Interest and Sources of Funding: The authors do not have any conflicts of interest to declare. This work was supported by NIH (P50 GM060338, R01 GM056687, R01 HD049471, R01 GM112936, R01-GM56687 and T32 GM008256), NIDILRR (H133A120091, 90DP00430100), Shriners Hospitals for Children (84080, 79141, 79135, 71009, 80100, 71008, 87300 and 71000), FAER (MRTG CON14876), and the Department of Defense (W81XWH-14-2-0162 and W81XWH1420162). It was also made possible with the support of UTMB’s Institute for Translational Sciences, supported in part by a Clinical and Translational Science Award (UL1TR000071) from the National Center for Advancing Translational Sciences (NIH).

Physician-Directed Versus Computerized Closed-Loop Control of Blood Pressure Using Phenylephrine in a Swine Model

BACKGROUND: Vasopressors provide a rapid and effective approach to correct hypotension in the perioperative setting. Our group developed a closed-loop control (CLC) system that titrates phenylephrine (PHP) based on the mean arterial pressure (MAP) during general anesthesia. As a means of evaluating system competence, we compared the performance of the automated CLC with physicians. We hypothesized that our CLC algorithm more effectively maintains blood pressure at a specified target with less blood pressure variability and reduces the dose of PHP required. METHODS: In a crossover study design, 6 swine under general anesthesia were subjected to a normovolemic hypotensive challenge induced by sodium nitroprusside. The physicians (MD) manually changed the PHP infusion rate, and the CLC system performed this task autonomously, adjusted every 3 seconds to achieve a predetermined MAP. RESULTS: The CLC maintained MAP within 5 mm Hg of the target for (mean ± standard deviation) 93.5% ± 3.9% of the time versus 72.4% ± 26.8% for the MD treatment (P = .054). The mean (standard deviation) percentage of time that the CLC and MD interventions were above target range was 2.1% ± 3.3% and 25.8% ± 27.4% (P = .06), respectively. Control statistics, performance error, median performance error, and median absolute performance error were not different between CLC and MD interventions. PHP infusion rate adjustments by the physician were performed 12 to 80 times in individual studies over a 60-minute period. The total dose of PHP used was not different between the 2 interventions. CONCLUSIONS: The CLC system performed as well as an anesthesiologist totally focused on MAP control by infusing PHP. Computerized CLC infusion of PHP provided tight blood pressure control under conditions of experimental vasodilation.

Automatic Control of Arterial Pressure for Hypotensive Patients using Phenylephrine

Abstract Developed in this paper is an automated closed-loop system that regulates the target blood pressure and maintains haemodynamic stability in hypotensive patients using the vasopressor drug phenylephrine. First, experimental studies are conducted on several healthy swine to identify dynamic mathematical models that quantify and predict blood pressure response to infusion of vasopressors. A first-order plus time-delay model structure has been selected to capture mean arterial pressure (MAP) response of patient’s subject to drug injection. Intra- and inter-patient variabilities of the model parameters have been identified and characterized. Then, an anti-windup proportional integral controller is designed, taking patient response variation in account. A nonlinear stochastic simulation environment has been developed to investigate the controller under diverse scenarios. Finally, automatic control of blood pressure is applied for the treatment of eight anesthetized swine subjected to hypotension induced by standard haemorrhage, spinal cord injury, and vasodilator injection. Results from clinical evaluations show that the proposed automated closed-loop control system is able to keep MAP near target and its performance is superior to that of manual control of infusion.

A prospective case series evaluating use of an in-line air detection and purging system to reduce air burden during major surgery

BackgroundIntravascular air embolism (AE) is a preventable but potentially catastrophic complication caused by intravenous tubing, trauma, and diagnostic and surgical procedures. The potentially fatal risks of arterial AE are well-known, and emerging evidence demonstrates impact of venous AEs on inflammatory response and coagulation factors. A novel FDA-approved in-line air detection and purging system was used to detect and remove air caused by administering a rapid fluid bolus during surgery.MethodsA prospective, randomized, case series was conducted. Subjects were observed using standard monitors, including transesophageal echocardiography (TEE) in the operating room. After general anesthesia was induced, an introducer and pulmonary artery catheter was inserted in the right internal jugular to administer fluids and monitor cardiac pressures. Six patients undergoing cardiac surgery were studied. Each patient received four randomized fluid boluses: two with the in-line air purging device, two without. For each bolus, a bulb infuser was squeezed three times (10–15 mL) over 5 s. The TEE was positioned in the mid-esophageal right atrium (RA) to quantify peak air clearance, and images were video recorded throughout each bolus. Air was quantified using optical densitometry (OD) from images demonstrating maximal air in the RA.ResultsAll subjects demonstrated significantly lower air burden when the air reduction device was used (p = 0.004), and the average time to clear 90% of air was also lower, 3.7 ± 1.2 s vs. 5.3 ± 1.3 s (p < 0.001).ConclusionAn air purging system reduced air burden from bolus administration and could consequently reduce the risk of harmful or fatal AEs during surgery.

Effectiveness of Colonic Fluid Resuscitation in a Burn-Injured Swine

To determine the effectiveness of colonic fluid absorption as a route for fluid resuscitation of a major burn. In order to assess the feasibility and performance of colonic resuscitation, the authors compared plasma volume expansion and hemodynamic parameters of animals submitted to colonic or intravenous fluid resuscitation. Twelve anesthetized swine were submitted to a 40% full thickness flame burn. Thirty minutes later fluid resuscitation was initiated with either intravenous or colonic infusion of crystalloid based on the Parkland formula. This treatment lasted 4.5 hours. The volume of fluid infused was 86 ± 18 ml/kg for the intravenous treatment and 89 ± 14 ml/kg for the colonic treatment. The percentage of fluid absorbed by the colon at the end of the protocol was 30 ± 13% of the infused fluid. Enteral resuscitation was equally effective in expanding plasma volume at the end of the protocol. Laboratorial and hemodynamic parameters were similar between the two resuscitation strategies throughout the study. Urine output was significantly higher in the intravenous group (7.9 ± 4.2 ml/kg/hr vs 0.9 ± 0.3 ml/kg/hr, P = .03). This study demonstrates that colonic infusion of normal saline in a severe burn injury model can restore hemodynamic stability and expand plasma volume to a degree that rivals the effect of direct intravenous infusion for early burn resuscitation in a swine model.

Multivariate physiological recordings in an experimental hemorrhage model

In this paper we describe a data set of multivariate physiological measurements recorded from conscious sheep (N = 8; 37.4 ± 1.1 kg) during hemorrhage. Hemorrhage was experimentally induced in each animal by withdrawing blood from a femoral artery at two different rates (fast: 1.25 mL/kg/min; and slow: 0.25 mL/kg/min). Data, including physiological waveforms and continuous/intermittent measurements, were transformed to digital file formats (European Data Format [EDF] for waveforms and Comma-Separated Values [CSV] for continuous and intermittent measurements) as a comprehensive data set and stored and publicly shared here (Appendix A). The data set comprises experimental information (e.g., hemorrhage rate, animal weight, event times), physiological waveforms (arterial and central venous blood pressure, electrocardiogram), time-series records of non-invasive physiological measurements (SpO2, tissue oximetry), intermittent arterial and venous blood gas analyses (e.g., hemoglobin, lactate, SaO2, SvO2) and intermittent thermodilution cardiac output measurements. A detailed explanation of the hemodynamic and pulmonary changes during hemorrhage is available in a previous publication (Scully et al., 2016) [1].