Background Hemorrhagic shock is the leading cause of trauma-related death in the military setting. Definitive surgical treatment of a combat casualty can be delayed and life-saving fluid resuscitation might be necessary in the field. Therefore, improved resuscitation strategies are critically needed for prolonged field and en route care. We developed an automated closed-loop control system capable of titrating fluid infusion to a target endpoint. We used the system to compare the performance of a decision table algorithm (DT) and a fuzzy logic controller (FL) to rescue and maintain the mean arterial pressure (MAP) at a target level during hemorrhages. Fuzzy logic empowered the control algorithm to emulate human expertise. We hypothesized that the FL controller would be more effective and more efficient than the DT algorithm by responding in a more rigid, structured way.MethodsTen conscious sheep were submitted to a hemorrhagic protocol of 25 ml/kg over three separate bleeds. Automated resuscitation with lactated Ringer’s was initiated 30 min after the first hemorrhage started. The endpoint target was MAP. Group differences were assessed by two-tailed t test and alpha of 0.05.ResultsBoth groups maintained MAP at similar levels throughout the study. However, the DT group required significantly more fluid than the FL group, 1745 ± 552 ml (42 ± 11 ml/kg) versus 978 ± 397 ml (26 ± 11 ml/kg), respectively (p = 0.03).ConclusionThe FL controller was more efficient than the DT algorithm and may provide a means to reduce fluid loading. Effectiveness was not different between the two strategies. Automated closed-loop resuscitation can restore and maintain blood pressure in a multi-hemorrhage model of shock.

BackgroundSepsis, 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.MethodsSubjects 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.FindingsSixty-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.InterpretationSevere 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.FundingConflicts 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).

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.

Objectives We sought to evaluate the efficacy, efficiency and physiological consequences of automated, end-point 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 (BR) 2) semi-autonomous (decision-assist, DA) fluid administration and 3) fully autonomous (closed-loop, CL) resuscitation. Hemodynamic parameters, 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 BP by 60 min. Following hemorrhage, the total amount of infused fluid (BR: 30ml/kg, DA: 5.6±3 ml/kg, CL: 4.2±2ml/kg, p<0.001), plasma volume, extravascular volume (BR: 17±4ml/kg, DA: 3±1ml/kg, CL: -0.3±0.3ml/kg, p<0.001), body weight and urinary output remained stable under DA and CL and were significantly increased under bolus resuscitation. Mean arterial pressure initially decreased further under bolus resuscitation (-10mmHg, p<0.001) and was lower under BR than CL at 20min (BR: 57±2mmHg CL: 69±4mmHg, p=0.036). Colloid-osmotic pressure (BR: 19.3±2mmHg DA, CL: 24±0.4mmHg, 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 to 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.

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