Closed-loop Fluid Research Articles

A GENERATIVE APPROACH TO TESTING THE PERFORMANCE OF PHYSIOLOGICAL CONTROL ALGORITHMS.

Physiological closed-loop control algorithms play an important role in the development of autonomous medical care systems, a promising area of research that has the potential to deliver healthcare therapies meeting each patient's specific needs. Computational approaches can support the evaluation of physiological closed-loop control algorithms considering various sources of patient variability that they may be presented with. In this paper, we present a generative approach to testing the performance of physiological closed-loop control algorithms. This approach exploits a generative physiological model (which consists of stochastic and dynamic components that represent diverse physiological behaviors across a patient population) to generate a select group of virtual subjects. By testing a physiological closed-loop control algorithm against this select group, the approach estimates the distribution of relevant performance metrics in the represented population. We illustrate the promise of this approach by applying it to a practical case study on testing a closed-loop fluid resuscitation control algorithm designed for hemodynamic management. In this context, we show that the proposed approach can test the algorithm against virtual subjects equipped with a wide range of plausible physiological characteristics and behavior, and that the test results can be used to estimate the distribution of relevant performance metrics in the represented population. In sum, the generative testing approach may offer a practical, efficient solution for conducting pre-clinical tests on physiological closed-loop control algorithms.

APRTC: advanced precise rapid thermal cycling in blow molding by applying fuzzy controller on thermoelectric devices for cooling and heating applications

This study presents an innovative approach to enhance thermal control in the blow molding production process, specifically focusing on achieving rapid and precise temperature regulation. To address the significant time consumption during mold closure, strategically deploying thermoelectric modules (TEMs) arranged according to the mold’s geometry enables meticulous temperature monitoring through integrated thermocouples. The configuration forms a matrix of interconnected TEMs, thermocouples, and controllers, orchestrating precise temperature adjustments across the mold surface. The research integrates fuzzy algorithms to facilitate seamless communication between thermoelectric devices and thermocouples for precise mold temperature control. Simulation of thermoelectric devices using COMSOL Multiphysics and implementation of fuzzy controllers in Matlab, connected through a live-link, enables real-time. I have adjustments and precise control. This integrated approach allows for a comprehensive analysis and optimization of the thermal control system, ensuring effective and adaptive temperature regulation. TEMs, operating as solid-state heat pumps, offer size versatility, adaptability to diverse mold shapes, and maintenance-free operation. Leveraging individual control capabilities significantly enhances heat transfer resolution, enabling precise manipulation of heat flux. Emphasizing the reduction of cooling time and achieving high-gloss surface quality, the study introduces the Advanced Precise Rapid Thermal Cycling in Blow Molding (APRTC) method. APRTC strategically employs TEMs to expedite cooling and elevate temperature determination accuracy, guaranteeing enhanced temperature resolution on the core mold surface. Furthermore, the study optimizes energy utilization through a closed-loop fluid circulation system, harnessing waste energy from other stages. Comparative analysis highlights APRTC's superiority, revealing a remarkable 91%\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$91 \\%$$\\end{document} reduction in temperature differentials during the cooling cycle and an 89%\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$89 \\%$$\\end{document} decrease in the heating stage. These findings underscore APRTC's efficacy in maintaining minimal temperature variations throughout the entire molding process.

Robust output-feedback control of fluid resuscitation with absolute stability guarantee against uncertain physiology and therapeutic responsiveness

This paper presents a robust closed-loop control approach to fluid resuscitation in patients with hemorrhagic blood loss. A unique strength of the proposed approach is its robustness against uncertain and time-varying patient physiology and therapeutic effectiveness. First, we adopted an observer-based control architecture that can fulfill set point tracking and disturbance rejection objectives. Second, we determined the control gains to achieve adequate transient response performance using the linear quadratic regulator design. Third, we determined the observer gains as a solution to a set of linear matrix inequalities so that the overall closed-loop fluid resuscitation control system is (i) robust against the variability in patient physiology and (ii) absolutely stable against unknown therapeutic effectiveness. We demonstrated the initial proof-of-concept of the proposed approach by conducting rigorous in silico testing using a large number of physiologically plausible virtual patients, while ascertaining the absolute stability via the circle criterion analysis. The results suggested that the proposed approach to closed-loop control of fluid resuscitation is a promising option to advance automation of fluid resuscitation armed with stability against a large variability in patient physiology and therapeutic effectiveness as well as adequate performance in set point tracking and disturbance rejection.

Air quality impacts from the development of unconventional oil and gas well pads: Air toxics and other volatile organic compounds

Unconventional oil and natural gas development (UOGD) has expanded rapidly across the United States in recent decades and raised concerns about associated air quality impacts. While significant effort has been made to quantify methane emissions, relatively few observations have been made of Volatile Organic Compounds (VOCs), especially during drilling and completion of new wells. Extensive air monitoring during development of several large, multi-well pads in Broomfield, Colorado, in the Denver-Julesburg Basin, provides a novel opportunity to examine changes in local air toxics and other VOC concentrations during well drilling and completions and production. These operations offer an especially useful case to study as several management practices were implemented to reduce emissions (e.g., electrified, grid-powered drill rigs and closed loop fluid handling systems to reduce truck traffic and limit fluid handling on the pad). With simultaneous measurements of methane and 50 VOCs from October 2018 to December 2022 at as many as 19 sites near well pads, in adjacent neighborhoods, and at a more distant reference location, we identify impacts from each phase of well development and production. Use of weekly, time-integrated canisters, a Proton Transfer Reaction Mass Spectrometer (PTR-MS), continuous photoionization detectors (PID) to trigger canister collection upon detection of VOC-rich plumes, and an instrumented vehicle, provided a powerful suite of measurements to characterize both transient plumes and longer-term changes in air quality. Prior to the start of well development, VOC gradients were small across Broomfield. Once drilling commenced, concentrations of oil and gas (O&G) related VOCs, including alkanes and aromatics, increased around active well pads. Concentration increases were clearly apparent during certain operations, including drilling, coil tubing/millout operations, and production tubing installation. Emissions of C8–C10 n-alkanes during drilling operations highlighted the importance of VOC emissions from synthetic drilling mud chosen to reduce odor impacts. More than 90 samples were collected of transient plumes. Using composition measurements, meteorological data, and information about well pad activities, these plumes were connected with specific UOGD operations including drilling, flowback, and production equipment maintenance. The chemical signatures of these plumes differed by operation type (e.g., C8–C10 n-alkanes constituted a larger fraction of measured VOCs in drilling-related plumes). Concentrations of individual, oil and gas-related VOCs in these plumes were often several orders of magnitude higher than in background air, with maximum ethane and benzene concentrations of 79,600 and 819 ppbv, respectively. Because these plumes typically impact a monitoring site for just several minutes, they are easily missed by slower-responding instruments. Study measurements highlight future emission mitigation opportunities during UOGD operations, including better control of emissions from shakers that separate drill cuttings from drilling mud, production separator maintenance operations, and periodic emptying of sand cans during flowback operations.

Closed-loop fluid–fluid immiscibility in binary lipid–sterol membranes

We present two binary lipid-sterol membrane systems that exhibit fluid-fluid coexistence. Partial phase diagrams of binary mixtures of dimyristoylphosphatidylcholine with 25-hydroxyxholesterol and 27-hydroxycholesterol, determined from small-angle X-ray scattering and fluorescence microscopy studies, show closed-loop fluid-fluid immiscibility gaps, with the appearance of a single fluid phase both at higher and lower temperatures. Computer simulations suggest that this unusual phase behavior results from the ability of these oxysterol molecules to take different orientations in the membrane depending on the temperature.

Techno-economic analysis of green energy resources for power generation & direct use by preserving near-wellbore geothermal gradient

Closed-loop fluid circulation in wellbores has gained considerable attention for harnessing the earth's thermal energy. Recent studies with analytical and numerical models show that geothermal gradient and well depth constitute the two most consequential variables in fluid output temperature at the surface. This study presents a new strategy for managing geothermal-gradient cooling to ensure more prolonged operation by adopting another energy source, such as solar or wind, with a day/night cycle over the years. In other words, the fluid circulation will occur at night, while the solar or wind source will operate in the daytime. Well-depth and geothermal gradients dictate which geographic area provides the best opportunity for power generation or hot water production to meet various industrial needs. Economic tools, such as Net Present Value and Levelized Cost of Electricity, helped gauge their strengths and limitations, thereby offering business decisions objectively.Considering a 20-year power generation period, this study provides some pragmatic lessons. For example, retaining the near-wellbore geothermal gradient is essential for assuring about 130 °C for the binary cycle. We can attain this objective with a 12-h fluid-circulation cycle by juxtaposing a second well or a solar/wind source for a day/night cycle. Also, besides being a safety net, a power grid can aid the economic value proposition in this energy-transition phase. The generation of hot water for direct industrial usage for low-geothermal prospects also becomes economically viable, particularly in repurposing abandoned wells. These industries include food and agriculture, requiring 60 to 85 °C.

Predicting fluid-response, the heart of hemodynamic management: A model-based solution

BackgroundIntravenous fluid infusions are an important therapy for patients with circulatory shock. However, it is challenging to predict how patients’ cardiac stroke volume (SV) will respond, and thus identify how much fluids should be delivered, if any. Model-predicted SV time-profiles of response to fluid infusions could potentially be used to guide fluid therapy. MethodA clinically applicable model-based method predicts SV changes in response to fluid-infusions for a pig trial (N = 6). Validation/calibration SV, SVmea, is from an aortic flow probe. Model parameters are identified in 3 ways: fitting to SVmea from the entire infusion, SVflfit, from the first 200 ml, SVfl200, or from the first 100 ml, SVfl100. RMSE compares error of model-based SV time-profiles for each parameter identification method, and polar plot analysis assesses trending ability. Receiver-operating characteristic (ROC) analysis evaluates ability of model-predicted SVs, SVfl200 and SVfl100, to distinguish non-responsive and responsive infusions, using area-under the curve (AUC), and balanced accuracy as a measure of performance. ResultsRMSE for SVflFit, SVfl200, and SVfl100 was 1.8, 3.2, and 6.5 ml, respectively, and polar plot angular limit of agreement from was 11.6, 28.0, and 68.8°, respectively. For predicting responsive and non-responsive interventions SVfl200, and SVfl100 had ROC AUC of 0.64 and 0.69, respectively, and balanced accuracy was 0.75 in both cases. ConclusionsThe model-predicted SV time-profiles matched measured SV trends well for SVflFit, SVfl200, but not SVfl100. Thus, the model can fit the observed SV dynamics, and can deliver good SV prediction given a sufficient parameter identification period. This trial is limited by small numbers and provides proof-of-method, with further experimental and clinical investigation needed. Potentially, this method could deliver model-predicted SV time-profiles to guide fluid therapy decisions, or as part of a closed-loop fluid control system.

Nonlinear reduced-order model for vertical sloshing by employing neural networks

The aim of this work is to provide a reduced-order model to describe the dissipative behavior of nonlinear vertical sloshing involving Rayleigh–Taylor instability by means of a feed forward neural network. A 1-degree-of-freedom system is taken into account as representative of fluid–structure interaction problem. Sloshing has been replaced by an equivalent mechanical model, namely a boxed-in bouncing ball with parameters suitably tuned with performed experiments. A large data set, consisting of a long simulation of the bouncing ball model with pseudo-periodic motion of the boundary condition spanning different values of oscillation amplitude and frequency, is used to train the neural network. The obtained neural network model has been included in a Simulink® environment for closed-loop fluid–structure interaction simulations showing promising performances for perspective integration in complex structural system.

Closed-Loop Control for Fluid Resuscitation: Recent Advances and Future Challenges.

Fluid therapy is extensively used to treat traumatized patients as well as patients during surgery. The fluid therapy process is complex due to interpatient variability in response to therapy as well as other complicating factors such as comorbidities and general anesthesia. These complexities can result in under- or over-resuscitation. Given the complexity of the fluid management process as well as the increased capabilities in hemodynamic monitoring, closed-loop fluid management can reduce the workload of the overworked clinician while ensuring specific constraints on hemodynamic endpoints are met with higher accuracy. The goal of this paper is to provide an overview of closed-loop control systems for fluid management and highlight several key steps in transitioning such a technology from bench to the bedside.

A numerical study on processes of charge and discharge of latent heat energy storage system using RT27 paraffin wax for exhaust waste heat recovery in a SI engine

In the present paper, the numerical analyses of the heat charge and discharge processes of the latent heat energy storage (LHTES) system designed for the recovery of the exhaust waste heat energy of the SI engine presented. In the LHTES system as phase change material (PCM), the charge and discharge ability of paraffin wax commercially identified with code RT27 were analyzed depending on time. Two closed-loop fluid circulation system consisting of two heat exchangers (HESs) was designed, someone connected to the exhaust path of SI engine for waste heat recovery, and the other used for the charging and discharging of waste heat energy in the PCM. To transfer the waste heat from the hot exhaust gases to the PC, cold water was used as the heat carrier fluid. In the numerical analysis, the exhaust gas temperature and flow rate values of a single-cylinder, air-cooled having a stroke volume of 476.5 cm3 SI engine operated with gasoline at 1600 rpm engine speed and 1/2 throttle position were used. As a result, at designed LHTES system and numerical analysis performed for RT27 paraffin wax under boundary conditions, the process of heat charge (melting) completed at 8000.sec with 93% liquid-fraction, while the process of heat discharge (solidification) completed at 55000.sec with 15% liquid-fraction.

Development and In Silico Evaluation of a Model-Based Closed-Loop Fluid Resuscitation Control Algorithm.

To develop and evaluate in silico a model-based closed-loop fluid resuscitation control algorithm via blood volume feedback. Model-based adaptive control algorithm for fluid resuscitation was developed by leveraging a low-order lumped-parameter blood volume dynamics model, and then in silico evaluated based on a detailed mechanistic model of circulatory physiology. The algorithm operates in two steps: (1) the blood volume dynamics model is individualized based on the patient's fractional blood volume response to an initial fluid bolus via system identification; and (2) an adaptive control law built on the individualized blood volume dynamics model regulates the blood volume of the patient. The algorithm was able to track the blood volume set point as well as accurately estimate and monitor the patient's absolute blood volume level. The algorithm significantly outperformed a population-based proportional-integral-derivative control. Model-based development of closed-loop fluid resuscitation control algorithm may enable regulation of blood volume and monitoring of absolute blood volume level. Model-based closed-loop fluid resuscitation algorithm may offer opportunities for standardized and patient-tailored therapy and reduction of clinician workload.

Control-oriented physiological modeling of hemodynamic responses to blood volume perturbation

This paper presents a physiological model to reproduce hemodynamic responses to blood volume perturbation. The model consists of three sub-models: a control-theoretic model relating blood volume response to blood volume perturbation; a simple physics-based model relating blood volume to stroke volume and cardiac output; and a phenomenological model relating cardiac output to blood pressure. A unique characteristic of this model is its balance for simplicity and physiological transparency. Initial validity of the model was examined using experimental data collected from 11 animals. The model may serve as a viable basis for the design and evaluation of closed-loop fluid resuscitation controllers.

Stronger at Depth: Jamming Grippers as Deep Sea Sampling Tools.

In this work we experimentally demonstrate (a) that the holding strength of universal jamming grippers increases as a function of the jamming pressure to greater than three atmospheres, and (b) that jamming grippers can be operated in the deep sea in ambient pressures exceeding one hundred atmospheres, where such high jamming pressures can be readily achieved. Laboratory experiments in a pressurized, water-filled test cell are used to measure the holding force of a "universal" style jamming gripper as a function of the pressure difference between internal membrane pressure and ambient pressure. Experiments at sea are used to demonstrate that jamming grippers can be installed on, and operated from, remotely operated vehicles at depths in excess of 1200 m. In both experiments, the jamming gripper consists of a latex balloon filled with a mixture of fresh water and ∼200 μm glass beads, which are cheaply available in large quantities as sand blasting media. The use of a liquid, rather than a gas, as the fluid media allows operation of the gripper with a closed-loop fluid system; jamming pressure is controlled with an electrically driven water hydraulic cylinder in the laboratory and with an oil hydraulic-driven large-bore water hydraulic cylinder at sea.

Closed-Loop Fluid Resuscitation Control Via Blood Volume Estimation

This paper presents a closed-loop control of fluid resuscitation to overcome hypovolemia based on model-based estimation of relative changes in blood volume (BV). In this approach, the control system consists of a model-based relative BV (RBV) estimator and a feedback controller. The former predicts relative changes in the BV response to augmented fluid by analyzing an arterial blood pressure (BP) waveform and the electrocardiogram (ECG). Then, the latter determines the amount of fluid to be augmented by comparing target versus predicted relative changes in BV. In this way, unlike many previous methods for fluid resuscitation based on controlled variable(s) nonlinearly correlated with the changes in BV, fluid resuscitation can be guided by a controlled variable linearly correlated with the changes in BV. This paper reports initial design of the closed-loop fluid resuscitation system and its in silico evaluation in a wide range of hypovolemic scenarios. The results suggest that closed-loop fluid resuscitation guided by a controlled variable linearly correlated with the changes in BV can be effective in overcoming hypovolemia: across 100 randomly produced hypovolemia cases, it resulted in the BV regulation error of 7.98 ± 171.6 ml, amounting to 0.18 ± 3.04% of the underlying BV. When guided by pulse pressure (PP), a classical controlled variable nonlinearly correlated with the changes in BV; the same closed-loop fluid resuscitation system resulted in persistent under-resuscitation with the BV regulation error of −779.1 ± 147.4 ml, amounting to −13.9 ± 2.65% of the underlying BV.

Perioperative goal directed therapy using automated closed-loop fluid management: the future?

 Although surgery has become much safer, it has also becoming increasingly more complex and perioperative complications continue to impact millions of patients worldwide each year. Perioperative hemodynamic optimization utilizing Goal Directed Therapy (GDT) has attracted considerable interest within the last decade due to its ability to improve postoperative short and long-term outcomes in patients undergoing higher risk surgeries. The concept of GDT in this context can be loosely defined as collecting data from minimally invasive hemodynamic monitors with the intention of using such data (flow-related parameters and/or dynamic parameters of fluid responsiveness) to titrate therapeutic interventions (intravenous fluids and/or inotropic therapy administration) with the ultimate aim of optimizing end organ tissue perfusion. Recently, the increasing amount of evidence supporting the implementation of GDT strategies has been considered so robust as to allow for the creation of national recommendations in the United Kingdom (UK), France, and Europe. These recommendations from such influential scientific societies and the potential clinical and economic benefits of GDT protocols need to also be examined within the current shift from a "pay for service" to a "pay for performance" health care system. This shift is strongly encouraged within emerging systems such as the Perioperative Surgical Home (PSH) paradigm from the United States. As a result, hospitals and clinicians around the world have become increasingly incentivized to implement perioperative hemodynamic optimization using GDT strategies within their departments. Unfortunately, its adoption continues to be quite limited and a lack of standardized criteria for perioperative fluid administrations has resulted in significant clinical variability among practitioners. This current review will provide a brief up-to-date overview of GDT, discuss current clinical practice, analyze why implementation has been limited and finally, describe the newer closed-loop GDT concept along with its potential risks and benefits.

Goal-Directed fluid therapy with closed-loop assistance during moderate risk surgery using noninvasive cardiac output monitoring: A pilot study

Goal directed fluid therapy (GDFT) has been shown to improve outcomes in moderate to high-risk surgery. However, most of the present GDFT protocols based on cardiac output optimization use invasive devices and the protocols may require significant practitioner attention and intervention to apply them accurately. The aim of this prospective pilot study was to evaluate the clinical feasibility of GDFT using a closed-loop fluid administration system with a non-invasive cardiac output monitoring device (Nexfin™, BMEYE, Amsterdam, Netherlands). Patients scheduled for elective moderate risk surgery under general anaesthesia were enrolled. The primary anaesthesia team managing the case selected GDFT targets using the controller interface and all patients received a baseline 3 ml kg(-1) h(-1) crystalloid infusion. Colloid solutions were delivered by the closed-loop system for intravascular volume expansion using data from the Nexfin™ monitor. Compliance with GDFT management was defined as acceptable when a patient spent more than 85% of the surgery time in a preload independent state (defined as pulse pressure variation <13%) or when average cardiac index during surgery was >2.5 litre min(-1) m(-2). A total of 13 patients were included in the study group. All patients met the established criteria for delivery of GDFT for greater than 85% of case time. The median length of stay in the hospital was 5 [3-6] days. In this pilot study, GDFT management using the closed-loop fluid administration system with a non-invasive CO monitoring device was feasible and maintained a high rate of protocol compliance. NCT02020863.

First closed-loop goal directed fluid therapy during surgery: A pilot study

ObjectiveIntraoperative haemodynamic optimization based on fluid management and stroke volume optimization (Goal Directed Fluid Therapy [GDFT]) can improve patients’ postoperative outcome. We have described a closed-loop fluid management system based on stroke volume variation and stroke volume monitoring. The goal of this system is to apply GDFT protocols automatically. After conducting simulation, engineering, and animal studies the present report describes the first use of this system in the clinical setting. Study designProspective pilot study. PatientsPatients undergoing major surgery. MethodsTwelve patients at two institutions had intraoperative GDFT delivered by closed-loop controller under the direction of an anaesthesiologist. Compliance with GDFT management was defined as acceptable when a patient spent more than 85% of the surgery time in a preload independent state (defined as stroke volume variation<13%), or when average cardiac index during the case was superior or equal to 2.5l/min/m2. ResultsClosed-loop GDFT was completed in 12 patients. Median surgery time was 447 [309–483] min and blood loss was 200 [100–1000] ml. Average cardiac index was 3.2±0.8l/min/m2 and on average patients spent 91% (76 to 100%) of the surgery time in a preload independent state. Twelve of 12 patients met the criteria for compliance with intraoperative GDFT management. ConclusionIntraoperative GDFT delivered by closed-loop system under anaesthesiologist guidance allowed to obtain targeted objectives in 91% of surgery time. This approach may provide a way to ensure consistent high-quality delivery of fluid administration and compliance with perioperative goal directed therapy.

Closed-Loop Systems in Anesthesia

Closed-Loop Systems in Anesthesia

Closed-Loop Fluid Resuscitation

Surgical patients present with a wide variety of body sizes and blood volumes, have large differences in baseline volume status, and may exhibit significant differences in cardiac function. Any closed-loop fluid administration system must be robust against these differences. In the current study, we tested the stability and robustness of the closed-loop fluid administration system against the confounders of body size, starting volume status, and cardiac contractility using control engineering methodology. Using an independently developed previously published hemodynamic simulation model that includes blood volumes and cardiac contractility, we ran a Monte-Carlo simulation series with variation in starting blood volume and body weight (phase 1, weight 35-100 kg), and starting blood volume and cardiac contractility (phase 2, contractility from 1500 [severe heart failure] to 6000 [hyperdynamic]). The performance of the controller in resuscitating to the target set point was evaluated in terms of milliliters of blood volume error from optimal, with <250 mL of error defined as "successful." One thousand simulations were run for each of the 2 phases of the study. The phase 1 mean blood volume error ± SD from optimal was 25 ± 59 mL. The phase 2 mean blood volume error from optimal was -60 ± 89 mL. The lower 95% Clopper-Pearson binomial confidence interval for resuscitation to within 250 mL of optimal blood volume for phase 1 and 2 was 99.6% and 97.1%, respectively. The results indicate that the controller is highly effective in targeting optimal blood and stroke volumes, regardless of weight, contractility or starting blood volume.

Closed-Loop Fluid Administration Compared to Anesthesiologist Management for Hemodynamic Optimization and Resuscitation During Surgery

Closed-loop systems have been designed to assist practitioners in maintaining stability of various physiologic variables in the clinical setting. In this context, we recently performed in silico testing of a novel closed-loop fluid management system that is designed for cardiac output and pulse pressure variation monitoring and optimization. The goal of the present study was to assess the effectiveness of this newly developed system in optimizing hemodynamic variables in an in vivo surgical setting. Sixteen Yorkshire pigs underwent a 2-phase hemorrhage protocol and were resuscitated by either the Learning Intravenous Resuscitator closed-loop system or an anesthesiologist. Median hemodynamic values and variation of hemodynamics were compared between groups. Cardiac index (in liters per minute per square meter) and stroke volume index (in milliliters per square meter) were higher in the closed-loop group compared with the anesthesiologist group over the protocol (3.7 [3.4-4.1] vs 3.5 [3.2-3.9]; 95% Wald confidence interval, -0.5 to -0.23; P < 0.0005 and 40 [34-45] vs 36 [31-38]; 95% Wald confidence interval, -5.9 to -3.1; P < 0.0005, respectively). There was no significant difference in total fluid administration between the closed-loop and anesthesiologist groups (3685 [3230-4418] vs 3253 [2735-3926] mL; 95% confidence interval, -1651 to 431; P = 0.28). Closed-loop group animals also had lower coefficients of variance of cardiac index and stroke volume index during the protocol (11% [10%-16%] vs 22% [18%-23%]; confidence interval, 0.8%-12.3%; P = 0.02 and 11% [8%-16%] vs 17% [13%-21%]; confidence interval, 0.2%-11.4%; P = 0.04, respectively). This in vivo study building on previous simulation work demonstrates that the closed-loop fluid management system used in this experiment can perform fluid resuscitation during mild and severe hemorrhages and is able to maintain high cardiac output and stroke volume while reducing hemodynamic variability.