A Lumped-Parameter Model of the Cardiovascular System Response for Evaluating Automated Fluid Resuscitation Systems.

Physiological closed-loop controlled (PCLC) medical devices, such as those designed for blood pressure regulation, can be tested for safety and efficacy in real-world clinical settings. However, relying solely on limited animal and clinical studies may not capture the diverse range of physiological conditions. Credible mathematical models can complement these studies by allowing the testing of the device against simulated patient scenarios.

Development and validation of a mathematical model of heart rate response to fluid perturbation.

Physiological closed-loop controlled (PCLC) medical devices monitor and automatically adjust the patient's condition by using physiological variables as feedback, ideally with minimal human intervention to achieve the target levels set by a clinician. PCLC devices present a challenge when it comes to evaluating their performance, where conducting large clinical trials can be expensive. Virtual physiological patients simulated by validated mathematical models can be utilized to obtain pre-clinical evidence of safety and assess the performance of the PCLC medical device during normal and worst-case conditions that are unlikely to happen in a limited clinical trial.

A Mathematical Model for Simulation of Vasoplegic Shock and Vasopressor Therapy.

Objective: To develop a high-fidelity mathematical model intended to replicate the cardiovascular (CV) responses of a critically ill patient to vasoplegic shock-induced hypotension and vasopressor therapy.

Methods: The mathematical model consists of a lumped-parameter CV physiology model with baroreflex modulation feedback and a phenomenological dynamic dose-response model of a vasopressor. The adequacy of the proposed mathematical model was investigated using an experimental dataset acquired from 10 pigs receiving phenylephrine (PHP) therapy after vasoplegic shock induced via sodium nitroprusside (SNP).

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.

Sex differences in the effects of adolescent intermittent ethanol exposure on exploratory and anxiety-like behavior in adult rats.

Adolescent intermittent ethanol (AIE) exposure in rodents has been shown to alter adult behavior in several domains, including learning and memory, social interaction, affective behavior, and ethanol self-administration. AIE has also been shown to produce non-specific behavioral changes that compromise behavioral efficiency. Many studies of these types rely on measuring behavior in mazes and other enclosures that can be influenced by animals' activity levels and exploratory behavior, and relatively few such studies have assessed sex as a biological variable.

Collective Variational Inference for Personalized and Generative Physiological Modeling: A Case Study on Hemorrhage Resuscitation.

Objective: Individual physiological experiments typically provide useful but incomplete information about a studied physiological process. As a result, inferring the unknown parameters of a physiological model from experimental data is often challenging. The objective of this paper is to propose and illustrate the efficacy of a collective variational inference (C-VI) method, intended to reconcile low-information and heterogeneous data from a collection of experiments to produce robust personalized and generative physiological models.

Mathematical Modeling, In-Human Evaluation and Analysis of Volume Kinetics and Kidney Function After Burn Injury and Resuscitation.

Objective: Existing burn resuscitation protocols exhibit a large variability in treatment efficacy. Hence, they must be further optimized based on comprehensive knowledge of burn pathophysiology. A physics-based mathematical model that can replicate physiological responses in diverse burn patients can serve as an attractive basis to perform non-clinical testing of burn resuscitation protocols and to expand knowledge on burn pathophysiology.

Accuracy assessment methods for physiological model selection toward evaluation of closed-loop controlled medical devices.

Physiological closed-loop controlled (PCLC) medical devices are complex systems integrating one or more medical devices with a patient's physiology through closed-loop control algorithms; introducing many failure modes and parameters that impact performance. These control algorithms should be tested through safety and efficacy trials to compare their performance to the standard of care and determine whether there is sufficient evidence of safety for their use in real care setting. With this aim, credible mathematical models have been constructed and used throughout the development and evaluation phases of a PCLC medical device to support the engineering design and improve safety aspects.

Mathematical model of volume kinetics and renal function after burn injury and resuscitation.

This paper presents a mathematical model of blood volume kinetics and renal function in response to burn injury and resuscitation, which is applicable to the development and non-clinical testing of burn resuscitation protocols and algorithms. Prior mathematical models of burn injury and resuscitation are not ideally suited to such applications due to their limited credibility in predicting blood volume and urinary output observed in wide-ranging burn patients as well as in incorporating contemporary knowledge of burn pathophysiology. Our mathematical model consists of an established multi-compartmental model of blood volume kinetics, a hybrid mechanistic-phenomenological model of renal function, and novel lumped-parameter models of burn-induced perturbations in volume kinetics and renal function equipped with contemporary knowledge on burn-related physiology and pathophysiology.

Fluid volumes infused during burn resuscitation 1980-2015: A quantitative review.

Introduction: 'Fluid creep' or excessive fluid delivered to burn patients during early resuscitation has been suggested by several studies from individual burn centers.

Methods: We performed a Medline search from 1980 to 2015 in order to identify studies of burn patients predominantly resuscitated with lactated Ringers with infusion adjusted per urinary output. Data was abstracted for 48 publications (3196 patients) that met entry criteria.

Operational Advantages of Enteral Resuscitation Following Burn Injury in Resource-Poor Environments: Palatability of Commercially Available Solutions.

Background: In recent combat operations, 5% to 15% of casualties sustained thermal injuries, which require resource-intensive therapies. During prolonged field care or when caring for patients in a multidomain battlefield, delayed transport will complicate the challenges that already exist in the burn population. A lack of resources and/or vascular access in the future operating environment may benefit from alternative resuscitation strategies.

The Medical Student Summer Research Program at the University of Texas Medical Branch at Galveston: building research foundations.

Background: Interest in incorporating research into the medical school curriculum has grown over the years. One of the challenges involved with providing research to medical students is developing programs that allow a large number of students to perform research. This involves securing faculty to mentor students in the design of research projects.

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.

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.

Multivariate physiological recordings in an experimental hemorrhage model.

In this paper we describe a data set of multivariate physiological measurements recorded from conscious sheep ( = 8; 37.4 ± 1.1 kg) during hemorrhage.

In-human subject-specific evaluation of a control-theoretic plasma volume regulation model.

The goal of this study was to conduct a subject-specific evaluation of a control-theoretic plasma volume regulation model in humans. We employed a set of clinical data collected from nine human subjects receiving fluid bolus with and without co-administration of an inotrope agent, including fluid infusion rate, plasma volume, and urine output. Once fitted to the data associated with each subject, the model accurately reproduced the fractional plasma volume change responses in all subjects: the error between actual versus model-reproduced fractional plasma volume change responses was only 1.

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.

Progression and variability of physiologic deterioration in an ovine model of lung infection sepsis.

In this study, a lung infection model of pneumonia in sheep ( = 12) that included smoke inhalation injury followed by methicillin-resistant placement into the lungs was used to investigate hemodynamic and pulmonary dysfunctions during the course of sepsis progression. To assess the variability in disease progression, animals were retrospectively divided into survivor ( = 6) and nonsurvivor ( = 6) groups, and a range of physiological indexes reflecting hemodynamic and pulmonary function were estimated and compared to evaluate variability in dynamics underlying sepsis development. Blood pressure and heart rate variability analyses were performed to assess whether they discriminated between the survivor and nonsurvivor groups early on and after intervention.

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.

Automated closed-loop resuscitation of multiple hemorrhages: a comparison between fuzzy logic and decision table controllers in a sheep model.

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.

Burn Shock and Resuscitation: Proceedings of a Symposium Conducted at the Meeting of the American Burn Association, Chicago, IL, 21 April 2015.

The Special Interest Groups of the American Burn Association provide a forum for interested members of the multidisciplinary burn team to congregate and discuss matters of mutual interest. At the 47th Annual Meeting of the American Burn Association in Chicago, IL, the Fluid Resuscitation Special Interest Group sponsored a special symposium on burn resuscitation. The purpose of the symposium was to review the history, current status, and future direction of fluid resuscitation of patients with burn shock.

Predicting the proportion of full-thickness involvement for any given burn size based on burn resuscitation volumes.

Introduction: The depth of burn has been an important factor often overlooked when estimating the total resuscitation fluid needed for early burn care. The goal of this study was to determine the degree to which full-thickness (FT) involvement affected overall 24-hour burn resuscitation volumes.

Methods: We performed a retrospective review of patients admitted to our burn intensive care unit from December 2007 to April 2013, with significant burns that required resuscitation using our computerized decision support system for burn fluid resuscitation.