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. This research involves the development and validation of a low-order lumped-parameter mathematical model of the cardiovascular system's response to fluid perturbation. The model takes rates of hemorrhage and fluid infusion as inputs and provides hematocrit and blood volume, heart rate, stroke volume, cardiac output and mean arterial blood pressure as outputs. The model was calibrated using data from 27 sheep subjects, and its predictive capability was evaluated through a leave-one-out cross-validation procedure, followed by independent validation using 12 swine subjects. Our findings showed small model calibration error against the training dataset, with the normalized root-mean-square error (NRMSE) less than 10% across all variables. The mathematical model and virtual patient cohort generation tool demonstrated a high level of predictive capability and successfully generated a sufficient number of subjects that closely resembled the test dataset. The average NRMSE for the best virtual subject, across two distinct samples of virtual subjects, was below 12.7% and 11.9% for the leave-one-out cross-validation and independent validation dataset. These findings suggest that the model and virtual cohort generator are suitable for simulating patient populations under fluid perturbation, indicating their potential value in PCLC medical device evaluation.

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). RESULTS: Upon calibration, the mathematical model could (i) faithfully replicate the effects of PHP on dynamic changes in blood pressure (BP), cardiac output (CO), and systemic vascular resistance (SVR) (root-mean-squared errors between measured and calibrated mathematical responses: mean arterial BP 2.5+/-1.0 mmHg, CO 0.2+/-0.1 lpm, SVR 2.4+/-1.5 mmHg/lpm; r value: mean arterial BP 0.96+/-0.01, CO 0.65+/-0.45, TPR 0.92+/-0.10) and (ii) predict physiologically plausible behaviors of unmeasured internal CV variables as well as secondary baroreflex modulation effects. CONCLUSION: This mathematical model is perhaps the first of its kind that can comprehensively replicate both primary (i.e., direct) and secondary (i.e., baroreflex modulation) effects of a vasopressor drug on an array of CV variables, rendering it ideally suited to pre-clinical virtual evaluation of the safety and efficacy of closed-loop control algorithms for autonomous vasopressor administration once it is extensively validated. SIGNIFICANCE: This mathematical model architecture incorporating both direct and baroreflex modulation effects may generalize to serve as part of an effective platform for high-fidelity in silico simulation of CV responses to vasopressors during vasoplegic shock.

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. We suspect that this could be due to age-related changes in endothelial function-an organ controlling the transport of fluid and solutes. The capillary filtration coefficient (CFC) is an important determinant of fluid transport. The CFC can be measured in vivo, which provides a tool to estimate endothelial barrier function. We have previously shown that the CFC increases when giving a fluid bolus resulting in increased vascular and extravascular volume expansion, in young adults. This study aimed to compare the physiologic determinants of fluid distribution in young versus older adults so that clinicians can best optimize perioperative fluid therapy. METHODS: Ten healthy young volunteers (ages 21-35) and nine healthy older volunteers (ages 60-75) received a 10 mL/kg fluid bolus over the course of twenty minutes. Hemodynamics, systolic and diastolic heart function, fluid volumetrics and microcirculatory determinants were measured before, during, and after the fluid bolus. RESULTS: Diastolic function was reduced in older versus younger adults before and after fluid bolus (P < 0.01). Basal CFC and plasma oncotic pressure were lower in the older versus younger adults. Further, CFC did not increase in older adults following the fluid bolus, whereas it did in younger adults (p < 0.05). Cumulative urinary output, while lower in older adults, was not significantly different (p = 0.059). Mean arterial pressure and systemic vascular resistance were elevated in the older versus younger adults (p < 0.05). CONCLUSION: Older adults show a less reactive CFC to a fluid bolus, which could reduce blood to tissue transport of fluid. Diastolic dysfunction likely contributes to fluid maldistribution in older adults.

Comparison of the Quantra QPlus System With Thromboelastography in Cardiac Surgery.

OBJECTIVES: Use of viscoelastic testing, such as thromboelastography (TEG), is recommended in cardiac surgery to monitor coagulation and to guide the transfusion of blood products. The Quantra QPlus System is a novel point-of-care platform that uses ultrasonic pulses to characterize dynamic changes in viscoelastic properties of a blood sample during coagulation. Despite the ability to assess similar aspects of clot formation, limited studies addressing the interchangeability of viscoelastic testing parameters exist. The primary aim of the present study was to assess the correlation and agreement between Quantra and TEG5000 results using blood samples from cardiac surgery patients. DESIGN: Tertiary care, academic medical center. SETTING: Prospective observational study. PARTICIPANTS: Twenty-eight patients undergoing elective cardiac surgery undergoing cardiopulmonary bypass were evaluated. MEASUREMENTS AND MAIN RESULTS: Perioperative blood samples were collected and assessed using Quantra, and results were compared with TEG and conventional coagulation testing. Method comparison analysis demonstrated that Quantra parameters (Quantra clot time, clot stiffness, and fibrinogen contribution to clot stiffness) significantly correlated with TEG R and TEG G after induction of anesthesia, during cardiopulmonary bypass, and after rewarming (rs = 0.83, rs = 0.84, and rs = 0.73, respectively). However, Quantra parameters demonstrated poor agreement compared with equivalent TEG5000 parameters. CONCLUSIONS: The Quantra QPlus System significantly correlated with TEG5000, suggesting that this test may be used in a similar clinical context. Despite the strength of correlation between Quantra and TEG parameters, measurements are not interchangeable.

Simulating Surgical Skills in Animals: Systematic Review, Costs & Acceptance Analyses.

Background: Modern surgery demands high-quality and reproducibility. Due to new working directives, resident duty hours have been restricted and evidence exists that pure on-the-job training provides insufficient exposure. We hypothesize that supplemental simulations in animal models provide a realistic training to augment clinical experiences. This study reviews surgical training models, their costs and survey results illustrating academic acceptance. Methods: Animal models were identified by literature research. Costs were analyzed from multiple German and Austrian training programs. A survey on their acceptance was conducted among faculty and medical students. Results: 915 articles were analyzed, thereof 91 studies described in-vivo animal training models, predominantly for laparoscopy (30%) and microsurgery (24%). Cost-analysis revealed single-training costs between 307€ and 5,861€ depending on model and discipline. Survey results illustrated that 69% of the participants had no experience, but 66% would attend training under experienced supervision. Perceived public acceptance was rated intermediate by medical staff and students (4.26; 1-low, 10 high). Conclusion: Training in animals is well-established and was rated worth attending in a majority of a representative cohort to acquire key surgical skills, in light of reduced clinical exposure. Animal models may therefore supplement the training of tomorrow's surgeons to overcome limited hands-on experience until virtual simulations can provide such educational tools.

Cardiac Dysfunction in Severely Burned Patients: Current Understanding of Etiology, Pathophysiology, and Treatment.

Patients who experience severe burn injuries face a massive inflammatory response resulting in hemodynamic and cardiovascular complications. Even after immediate and appropriate resuscitation, removal of burn eschar and covering of open areas, burn patients remain at high risk for serious morbidity and mortality. As a result of the massive fluid shifts following the initial injury, along with large volume fluid resuscitation, the cardiovascular system is critically affected. Further, increased inflammation, catecholamine surge, and hypermetabolic syndrome impact cardiac dysfunction, which worsens outcomes of burn patients. This review aimed to summarize the current knowledge about the effect of burns on the cardiovascular system.A comprehensive search of the PubMed and Embase databases and manual review of articles involving effects of burns on the cardiovascular system was conducted.Many burn units use multimodal monitors (e.g., transpulmonary thermodilution) to assess hemodynamics and optimize cardiovascular function. Echocardiography is often used for additional evaluations of hemodynamically unstable patients to assess systolic and diastolic function. Due to its noninvasive character, echocardiography can be repeated easily, which allows us to follow patients longitudinally.The use of anabolic and anticatabolic agents has been shown to be beneficial for short- and long-term outcomes of burn survivors. Administration of propranolol (non-selective ß-receptor antagonist) or oxandrolone (synthetic testosterone) for up to 12 months post-burn counteracts hypermetabolism during hospital stay and improves cardiac function.A comprehensive understanding of how burns lead to cardiac dysfunction and new therapeutic options could contribute to better outcomes in this patient population.

Effects of adjunct testosterone on cardiac morphology and function in advanced cancers: an ancillary analysis of a randomized controlled trial.

BACKGROUND: Adjunct testosterone therapy improves lean body mass, quality of life, and physical activity in patients with advanced cancers; however, the effects of testosterone on cardiac morphology and function are unknown. Accordingly, as an ancillary analysis of a randomized, placebo-controlled trial investigating the efficacy of testosterone supplementation on body composition in men and women with advanced cancers, we explored whether testosterone supplementation could prevent or reverse left ventricular (LV) atrophy and dysfunction. METHODS: Men and women recently diagnosed with late stage (≥IIB) or recurrent head and neck or cervical cancer who were scheduled to receive standard of care chemotherapy or concurrent chemoradiation were administered an adjunct 7 week treatment of weekly intramuscular injections of either 100 mg testosterone (T, n = 1 M/5F) or placebo (P, n = 6 M/4F) in a double-blinded randomized fashion. LV morphology (wall thickness), systolic function (ejection fraction, EF), diastolic function (E/A; E'/E), arterial elastance (Ea), end-systolic elastance (Ees), and ventricular-arterial coupling (Ea/Ees) were assessed. RESULTS: No significant differences were observed in LV posterior wall thickness in placebo (pre: 1.10 ± 0.1 cm; post: 1.16 ± 0.2 cm; p = 0.11) or testosterone groups (pre: 0.99 ± 0.1 cm; post: 1.14 ± 0.20 cm; p = 0.22). Compared with placebo, testosterone significantly improved LVEF (placebo: - 1.8 ± 4.3%; testosterone: + 6.2 ± 4.3%; p < 0.05), Ea (placebo: 0.0 ± 0.2 mmHg/mL; testosterone: - 0.3 ± 0.2 mmHg/mL; p < 0.05), and Ea/Ees (placebo: 0.0 ± 0.1; testosterone: - 0.2 ± 0.1; p < 0.05). CONCLUSIONS: In patients with advanced cancers, testosterone was associated with favorable changes in left ventricular systolic function, arterial elastance, and ventricular-arterial coupling. Given the small sample size, the promising multisystem benefits of testosterone warrants further evaluation in a definitive randomized trial. TRIAL REGISTRATION: This study was prospectively registered on ClinicalTrials.gov (NCT00878995; date of registration: April 9, 2009).

Blood Loss and Visibility with Esmolol vs Labetalol in Endoscopic Sinus Surgery: A Randomized Clinical Trial.

OBJECTIVES: Improved intraoperative visibility during functional endoscopic sinus surgery (FESS) decreases the risk of serious orbital or skull base injuries. Esmolol and labetalol have been used to reduce bleeding and achieve better visibility, but it remains unclear which drug is more effective. This study aims to measure visibility scores and mucosal bleeding rates for esmolol and labetalol in FESS. METHODS: This is a 1-year randomized double-blind trial of adults undergoing FESS at a tertiary academic center. The inclusion criteria were as follows: age 18 or older; history of chronic rhinosinusitis (CRS) with or without nasal polyps; undergoing FESS for CRS; and American Society of Anesthesiologists (ASA) physical status 1 (healthy) or 2 (patient with mild systemic disease). The exclusion criteria were as follows: pregnancy; asthma, chronic obstructive pulmonary disease (COPD), bradycardia, heart failure, end-stage renal disease, cerebrovascular accident, diabetes mellitus; preoperative use of nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, or beta-blockers; and body mass index (BMI) greater than 40 kg/m2. Patients received either dose-infused esmolol or intravenous push labetalol. The primary outcome was intraoperative visibility determined by surgeon using validated scoring systems (Boezaart, Wormald). The secondary outcome was hemodynamic control (rate of blood loss, average mean arterial pressure [MAP], average heart rate [HR]). Hypothesis of no difference between drugs formed before data collection. RESULTS: Of the 32 adults given drug (mean age = 50), 28 patients (13 esmolol and 15 labetalol) with complete data were included in the final analysis. There were no statistically significant differences between esmolol and labetalol in rate of blood loss (0.59 [0.28] vs 0.66 [0.37] mL/min, P = 0.62), average MAP (79.7 [7.5] vs 79.4 [7.7] mm Hg, P = .93), HR (72 [8.7] vs 68 [11.7] bpm, P = .26), or mean visibility scores for the Boezaart (3.1 [0.69] vs 3.1 [0.89], P = .85) and Wormald (6.1 [1.7] vs 5.9 [1.9], P = .72) grading scales. CONCLUSIONS: There were no significant differences between esmolol and labetalol in rate of blood loss, MAP control, HR, or surgical visibility in FESS. Either drug may be used, and other considerations (availability, cost) can dictate choice.

Population Kinetics of 0.9% Saline Distribution in Hemorrhaged Awake and Isoflurane-anesthetized Volunteers.

BACKGROUND: Population-based, pharmacokinetic modeling can be used to describe variability in fluid distribution and dilution between individuals and across populations. The authors hypothesized that dilution produced by crystalloid infusion after hemorrhage would be larger in anesthetized than in awake subjects and that population kinetic modeling would identify differences in covariates. METHODS: Twelve healthy volunteers, seven females and five males, mean age 28 ± 4.3 yr, underwent a randomized crossover study. Each subject participated in two separate sessions, separated by four weeks, in which they were assigned to an awake or an anesthetized arm. After a baseline period, hemorrhage (7 ml/kg during 20 min) was induced, immediately followed by a 25 ml/kg infusion during 20 min of 0.9% saline. Hemoglobin concentrations, sampled every 5 min for 60 min then every 10 min for an additional 120 min, were used for population kinetic modeling. Covariates, including body weight, sex, and study arm (awake or anesthetized), were tested in the model building. The change in dilution was studied by analyzing area under the curve and maximum plasma dilution. RESULTS: Anesthetized subjects had larger plasma dilution than awake subjects. The analysis showed that females increased area under the curve and maximum plasma dilution by 17% (with 95% CI, 1.08 to 1.38 and 1.07 to 1.39) compared with men, and study arm (anesthetized increased area under the curve by 99% [0.88 to 2.45] and maximum plasma dilution by 35% [0.71 to 1.63]) impacted the plasma dilution whereas a 10-kg increase of body weight resulted in a small change (less than1% [0.93 to 1.20]) in area under the curve and maximum plasma dilution. Mean arterial pressure was lower in subjects while anesthetized (P < 0.001). CONCLUSIONS: In awake and anesthetized subjects subjected to controlled hemorrhage, plasma dilution increased with anesthesia, female sex, and lower body weight. Neither study arm nor body weight impact on area under the curve or maximum plasma dilution were statistically significant and therefore no effect can be established.

Functional Improvements Utilizing the Short Physical Performance Battery (SPPB) in the Elderly after Epidural Steroid Injections.

PURPOSE OF REVIEW: The treatment of debilitating pain and loss of function secondary to lumbar stenosis is in high demand with the aging patient population. Options, including epidural steroid injections (ESIs) and medication therapy, are limited and it is unclear if they provide any functional improvements. In this prospective study, we evaluate functional outcomes in older adults with symptomatic lumbar stenosis treated with ESIs compared to those managed with medications by introducing the Short Physical Performance Battery (SPPB). Our study was IRB-approved and included 16 patients, 68 to 83 years old, with symptomatic back and radicular leg pain secondary to lumbar stenosis. Patients could elect to undergo a lumbar ESI (n = 11) or be treated via medication management (n = 5). Numeric pain score, SPPB score, and adverse events were measured and compared at baseline and a 1-month follow-up visit. RECENT FINDINGS: Statistically significant improvements were observed from baseline compared to the 1-month follow-up for total SPPB score in the injection group. Similar improvements in the injection group were observed for pain scores and the SPPB subcomponents such as the 4-m walk test, chair stand time, and balance score. Comparatively, no statistically significant improvements were observed in the medication group. Lumbar ESIs improved objective physical capacity parameters and pain scores in elderly patients with symptomatic lumbar stenosis compared to medication management. In addition, the SPPB is an easy-to-use tool to measure changes in physical function in older adults and could easily be integrated into an outpatient pain clinic.

Diastolic Function and Peripheral Venous Pressure as Indices for Fluid Responsiveness in Cardiac Surgical Patients.

OBJECTIVE: Identifying fluid responsiveness is critical to optimizing perfusion while preventing fluid overload. An experimental study of hypovolemic shock resuscitation showed the importance of ventricular compliance and peripheral venous pressure (PVP) on fluid responsiveness. The authors tested the hypothesis that reduced ventricular compliance measured using transesophageal echocardiography results in decreased fluid responsiveness after a fluid bolus. DESIGN: Prospective observational study. SETTING: Two-center, university hospital study. PARTICIPANTS: The study comprised 29 patients undergoing elective coronary revascularization. INTERVENTION: Albumin 5%, 7 mL/kg, was infused over 10 minutes to characterize fluid responders (>15% increase in stroke volume) from nonresponders. MEASUREMENTS AND MAIN RESULTS: Invasive hemodynamics and the ratio of mitral inflow velocity (E-wave)/annular relaxation (e'), or E/e' ratio, were measured using transesophageal echocardiography to assess left ventricular (LV) compliance at baseline and after albumin infusion. Fifteen patients were classified as responders and 14 as nonresponders. The E/e' ratio in responders was 7.4 ± 1.9 at baseline and 7.1 ± 1.8 after bolus. In contrast, E/e' was significantly higher in nonresponders at baseline (10.7 ± 4.6; p = 0.04) and further increased after bolus (12.6 ± 5.5; p = 0.002). PVP was significantly greater in the nonresponders at baseline (14 ± 4 mmHg v 11 ± 3 mmHg; p = 0.02) and increased in both groups after albumin infusion. Fluid responsiveness was tested using the area under the receiver operating characteristic curve and was 0.74 for the E/e' ratio (95% confidence interval 0.55-0.93; p = 0.029) and 0.72 for the PVP (95% confidence interval 0.52-0.92; p = 0.058). CONCLUSION: Fluid responders had normal LV compliance and lower PVP at baseline. In contrast, nonresponders had reduced LV compliance, which worsened after fluid bolus. E/e,' more than PVP, may be a useful clinical index to predict fluid responsiveness.

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

BACKGROUND: Intravascular 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. METHODS: A 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. RESULTS: All 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). CONCLUSION: An air purging system reduced air burden from bolus administration and could consequently reduce the risk of harmful or fatal AEs during surgery.

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].

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.

Respiratory Volume Monitoring Reduces Hypoventilation and Apnea in Subjects Undergoing Procedural Sedation.

INTRODUCTION: The use of monitored anesthesia care for endoscopic procedures increases the risk of respiratory depression, necessitating careful monitoring of patient ventilation. We examined the effectiveness of an impedance-based respiratory volume monitor (RVM) in improving the safety of patients undergoing upper and lower gastrointestinal endoscopies under total intravenous anesthesia. We hypothesized that feedback from the RVM would allow anesthesiologists to maintain adequate ventilation, which would reduce the duration of respiratory depression (ie, hypoventilation and apnea) compared to a blinded control group. METHODS: Sixty-five subjects were enrolled in a randomized controlled trial and monitored with a noninvasive impedance-based RVM, which displayed respiratory traces and calculated expiratory minute ventilation (V̇E), tidal volume (VT), and breathing frequency (f) measurements. Prior to induction of anesthesia, a baseline V̇E measurement (V̇E-baseline) was taken as a measurement of normal breathing. V̇E was monitored throughout the procedure for signs of hypoventilation and apnea. Hypoventilation was defined as V̇E < 40% V̇E-baseline, and apneas were defined as V̇E = 0 for > 15 s. RESULTS: Sixty-five subjects were randomly assigned to either a control (n = 38) or RVM intervention group (n = 27). Subjects in the intervention group had a higher V̇E% for the entire procedure (P = .045), as well as the third and fourth quartile of the procedure compared to the control group (P = .01). Likewise, subjects in the RVM intervention group spent significantly less time below 40% V̇E-baseline compared to the control group throughout the entire procedure (12 ± 15% vs 32 ± 24%, respectively) (P < .001). The median number of apneas per subject was greater in the control group (median 2, interquartile range 1-2, maximum 4) compared to the RVM intervention group (median 1, interquartile range 1-2, maximum 3) (P = .037). CONCLUSIONS: The control group had a higher incidence of hypoventilation and apnea compared to the RVM intervention group. Respiratory monitoring using the RVM can potentially be a useful tool for identifying early signs of respiratory depression and for titrating anesthetics to maintain adequate ventilation while minimizing patient risk.

Co-administration of vancomycin and piperacillin-tazobactam is associated with increased renal dysfunction in adult and pediatric burn patients.

BACKGROUND: Burn patients are prone to infections which often necessitate broad antibiotic coverage. Vancomycin is a common antibiotic after burn injury and is administered alone (V), or in combination with imipenem-cilastin (V/IC) or piperacillin-tazobactam (V/PT). Sparse reports indicate that the combination V/PT is associated with increased renal dysfunction. The purpose of this study was to evaluate the short-term impact of the three antibiotic administration types on renal dysfunction. METHODS: All pediatric and adult patients admitted to our centers between 2004 and 2016 with a burn injury were included in this retrospective review if they met the criteria of exposition to either V, V/IC, or V/PT for at least 48 h, had normal baseline creatinine, and no pre-existing renal dysfunction. Creatinine was monitored for 7 days after initial exposure; the absolute and relative increase was calculated, and patient renal outcomes were classified according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria depending on creatinine increases and estimated creatinine clearance. Secondary endpoints (demographic and clinical data, incidences of septicemia, and renal replacement therapy) were analyzed. Antibiotic doses were modeled in logistic and linear multivariable regression models to predict categorical KDIGO events and relative creatinine increase. RESULTS: Out of 1449 patients who were screened, 718 met the inclusion criteria, 246 were adults, and 472 were children. Between the study cohorts V, V/IC, and V/PT, patient characteristics at admission were comparable. V/PT administration was associated with a statistically higher serum creatinine, and lower creatinine clearance compared to patients receiving V alone or V/IC in adults and children after burn injury. The incidence of KDIGO stages 1, 2, and 3 was higher after V/PT treatment. In children, the incidence of KDIGO stage 3 following administration of V/PT was greater than after V/IC. In adults, the incidence of renal replacement therapy was higher after V/PT compared with V or V/IC. Multivariate modeling demonstrated that V/PT is an independent predictor of renal dysfunction. CONCLUSION: Co-administration of vancomycin and piperacillin-tazobactam is associated with increased renal dysfunction in pediatric and adult burn patients when compared to vancomycin alone or vancomycin plus imipenem-cilastin. The mechanism of this increased nephrotoxicity remains elusive and warrants further scientific evaluation.

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 1.4 ± 1.6% and 1.2 ± 0.3% of the average fractional plasma volume change responses in the absence and presence of inotrope co-administration. In addition, the model parameters determined by the subject-specific fitting assumed physiologically plausible values: (i) initial plasma volume was estimated to be 36 ± 11 mL/kg and 37 ± 10 mL/kg in the absence and presence of inotrope infusion, respectively, which was comparable to its actual counterpart of 37 ± 4 mL/kg and 43 ± 6 mL/kg; (ii) volume distribution ratio, specifying the ratio with which the inputted fluid is distributed in the intra- and extra-vascular spaces, was estimated to be 3.5 ± 2.4 and 1.9 ± 0.5 in the absence and presence of inotrope infusion, respectively, which accorded with the experimental observation that inotrope could enhance plasma volume expansion in response to fluid infusion. We concluded that the model was equipped with the ability to reproduce plasma volume response to fluid infusion in humans with physiologically plausible model parameters, and its validity may persist even under co-administration of inotropic agents.