Long-duration spaceflight alters estimated intracranial pressure and cerebral blood velocity.

KEY POINTS: During long-duration spaceflights, some astronauts develop structural ocular changes including optic disc oedema that resemble signs of intracranial hypertension. In the present study, intracranial pressure was estimated non-invasively (nICP) using a model-based analysis of cerebral blood velocity and arterial blood pressure waveforms in 11 astronauts before and after long-duration spaceflights. Our results show that group-averaged estimates of nICP decreased significantly in nine astronauts without optic disc oedema, suggesting that the cephalad fluid shift during long-duration spaceflight rarely increased postflight intracranial pressure. The results of the two astronauts with optic disc oedema suggest that both increases and decreases in nICP are observed post-flight in astronauts with ocular alterations, arguing against a primary causal relationship between elevated ICP and spaceflight associated optical changes. Cerebral blood velocity increased independently of nICP and spaceflight-associated ocular alterations. This increase may be caused by the reduced haemoglobin concentration after long-duration spaceflight. ABSTRACT: Persistently elevated intracranial pressure (ICP) above upright values is a suspected cause of optic disc oedema in astronauts. However, no systematic studies have evaluated changes in ICP from preflight. Therefore, ICP was estimated non-invasively before and after spaceflight to test whether ICP would increase after long-duration spaceflight. Cerebral blood velocity in the middle cerebral artery (MCAv) was obtained by transcranial Doppler sonography and arterial pressure in the radial artery was obtained by tonometry, in the supine and sitting positions before and after 4-12 months of spaceflight in 11 astronauts (10 males and 1 female, 46 ± 7 years old at launch). Non-invasive ICP (nICP) was computed using a validated model-based estimation method. Mean MCAv increased significantly after spaceflight (ANOVA, P = 0.007). Haemoglobin decreased significantly after spaceflight (14.6 ± 0.8 to 13.3 ± 0.7 g/dL, P < 0.001). A repeated measures correlation analysis indicated a negative correlation between haemoglobin and mean MCAv (r = -0.589, regression coefficient = -4.68). The nICP did not change significantly after spaceflight in the 11 astronauts. However, nICP decreased significantly by 15% in nine astronauts without optic disc oedema (P < 0.005). Only one astronaut increased nICP to relatively high levels after spaceflight. Contrary to our hypothesis, nICP did not increase after long-duration spaceflight in the vast majority (>90%) of astronauts, suggesting that the cephalad fluid shift during spaceflight does not systematically or consistently elevate postflight ICP in astronauts. Independently of nICP and ocular alterations, the present results of mean MCAv suggest that long-duration spaceflight may increase cerebral blood flow, possibly due to reduced haemoglobin concentration.

Cerebral Emboli Monitoring Using Transcranial Doppler Ultrasonography in Adults and Children: A Review of the Current Technology and Clinical Applications in the Perioperative and Intensive Care Setting.

Transcranial Doppler (TCD) ultrasonography is the only noninvasive bedside technology for the detection and monitoring of cerebral embolism. TCD may identify patients at risk of acute and chronic neurologic injury from gaseous or solid emboli. Importantly, a window of opportunity for intervention-to eliminate the source of the emboli and thereby prevent subsequent development of a clinical or subclinical stroke-may be identified using TCD. In this review, we discuss the application of TCD sonography in the perioperative and intensive care setting in adults and children known to be at increased risk of cerebral embolism. The major challenge for evaluation of emboli, especially in children, is the need to establish the ground truth and define true emboli identified by TCD. This requires the development and validation of a predictive TCD emboli monitoring technique so that appropriately designed clinical studies intended to identify specific modifiable factors and develop potential strategies to reduce pathologic cerebral embolic burden can be performed.

Intracranial Pressure and Intracranial Elastance Monitoring in Neurocritical Care.

Patients with acute brain injuries tend to be physiologically unstable and at risk of rapid and potentially life-threatening decompensation due to shifts in intracranial compartment volumes and consequent intracranial hypertension. Invasive intracranial pressure (ICP) monitoring therefore remains a cornerstone of modern neurocritical care, despite the attendant risks of infection and damage to brain tissue arising from the surgical placement of a catheter or pressure transducer into the cerebrospinal fluid or brain tissue compartments. In addition to ICP monitoring, tracking of the intracranial capacity to buffer shifts in compartment volumes would help in the assessment of patient state, inform clinical decision making, and guide therapeutic interventions. We review the anatomy, physiology, and current technology relevant to clinical management of patients with acute brain injury and outline unmet clinical needs to advance patient monitoring in neurocritical care.

Antibiotic Delays and Feasibility of a 1-Hour-From-Triage Antibiotic Requirement: Analysis of an Emergency Department Sepsis Quality Improvement Database.

STUDY OBJECTIVE: We identify factors associated with delayed emergency department (ED) antibiotics and determine feasibility of a 1-hour-from-triage antibiotic requirement in sepsis. METHODS: We studied all ED adult septic patients in accordance with Centers for Medicare & Medicaid Services Severe Sepsis and Septic Shock National Quality Measures in 2 consecutive 12-month intervals. During the second interval, a quality improvement intervention was conducted: a sepsis screening protocol plus case-specific feedback to clinicians. Data were abstracted retrospectively through electronic query and chart review. Primary outcomes were antibiotic delay greater than 3 hours from documented onset of hypoperfusion (per Centers for Medicare & Medicaid Services Severe Sepsis and Septic Shock National Quality Measures) and antibiotic delay greater than 1 hour from triage (per 2018 Surviving Sepsis Campaign recommendations). RESULTS: We identified 297 and 357 septic patients before and during the quality improvement intervention, respectively. Before and during quality improvement intervention, antibiotic delay in accordance with Centers for Medicare & Medicaid Services measures occurred in 30% and 21% of cases (-9% [95% confidence interval -16% to -2%]); and in accordance with 2018 Surviving Sepsis Campaign recommendations, 85% and 71% (-14% [95% confidence interval -20% to -8%]). Four factors were independently associated with both definitions of antibiotic delay: vague (ie, nonexplicitly infectious) presenting symptoms, triage location to nonacute areas, care before the quality improvement intervention, and lower Sequential [Sepsis-related] Organ Failure Assessment scores. Most patients did not receive antibiotics within 1 hour of triage, with the exception of a small subset post-quality improvement intervention who presented with explicit infectious symptoms and triage hypotension. CONCLUSION: The quality improvement intervention significantly reduced antibiotic delays, yet most septic patients did not receive antibiotics within 1 hour of triage. Compliance with the 2018 Surviving Sepsis Campaign would require a wholesale alteration in the management of ED patients with either vague symptoms or absence of triage hypotension.

Tracking autonomic balance using an open-loop model of the arterial baroreflex.

Blood pressure control is vital for maintaining adequate perfusion of the brain and other organs in the body across varying physiological demands, and the arterial baroreceptor reflex (baroreflex) is the major short-term blood pressure control loop mediated by the autonomic nervous system (ANS). Accurate quantitative models of the baroreflex would provide physiological insight and could allow for real-time tracking of ANS activity in clinical settings. In this work, we formulate a causal, parametric beat-to-beat model, relating systolic blood pressure (input) to heart rate (output). Model structure and parameterization are explicitly based on prior physiological insights of the response dynamics of the sympathetic and parasympathetic branches of the ANS. We analyze the model's ability to track changes in autonomic balance using data from 14 nonsmoking adult males, without any history of cardiopulmonary disease, subject to both pharmacological blockade and postural changes. Our results show that the model parameters faithfully track expected changes in autonomic balance resulting from changing posture ( P < 0.01) and sympathetic blockade ( P < 0.05), and in many cases, the model parameters are more sensitive to changes in autonomic activity and balance than autonomic indices derived from the power spectral density of heart rate variability. Overall, the contributions of this work further the goal of obtaining real-time quantitative assessment of the ANS.

Presenting Symptoms Independently Predict Mortality in Septic Shock: Importance of a Previously Unmeasured Confounder.

OBJECTIVES: Presenting symptoms in patients with sepsis may influence rapidity of diagnosis, time-to-antibiotics, and outcome. We tested the hypothesis that vague presenting symptoms are associated with delayed antibiotics and increased mortality. We further characterized individual presenting symptoms and their association with mortality. DESIGN: Retrospective cohort study. SETTING: Emergency department of large, urban, academic U.S. hospital. PATIENTS: All adult patients with septic shock treated in the emergency department between April 2014 and March 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 654 septic shock cases, 245 (37%) presented with vague symptoms. Time-to-antibiotics from first hypotension or elevated lactate was significantly longer for those with vague symptoms versus those with explicit symptoms of infection (1.6 vs 0.8 hr; p < 0.01), and in-hospital mortality was also substantially higher (34% vs 16%; p < 0.01). Patients with vague symptoms were older and sicker as evidenced by triage hypotension, Sequential Organ Failure Assessment score, initial serum lactate, and need for intubation. In multivariate analysis, vague symptoms were independently associated with mortality (adjusted odds ratio, 2.12; 95% CI, 1.32-3.40; p < 0.01), whereas time-to-antibiotics was not associated with mortality (adjusted odds ratio, 1.01; 95% CI, 0.94-1.08; p = 0.78). Of individual symptoms, only the absence of fever, chills, or rigors (odds ratio, 2.70; 95% CI, 1.63-4.47; p < 0.01) and presence of shortness of breath (odds ratio, 1.97; 95% CI, 1.23-3.15; p < 0.01) were independently associated with mortality. CONCLUSIONS: More than one third of patients with septic shock presented to the emergency department with vague symptoms that were not specific to infection. These patients had delayed antibiotic administration and higher risk of mortality even after controlling for demographics, illness acuity, and time-to-antibiotics in multivariate analysis. These findings suggest that the nature of presenting symptoms is an important component of sepsis clinical phenotyping and may be an important confounder in sepsis epidemiologic studies.

Blood Pressure Coefficient of Variation and Its Association With Cardiac Surgical Outcomes.

BACKGROUND: Multiple studies completed in the ambulatory nonsurgical setting show a significant association between short- and long-term blood pressure variability and poor outcomes. However, perioperative blood pressure variability outcomes have not been well studied, especially in the cardiac surgical setting. In this study, we sought to assess whether systolic and mean arterial blood pressure variability were associated with 30-day mortality and in-hospital renal failure in patients undergoing cardiac surgery requiring cardiopulmonary bypass. Furthermore, blood pressure variability has not been evaluated specifically during each phase of surgery, namely in the pre-, intra- and postbypass phases; thus, we aimed also to assess whether outcomes were associated with phase-specific systolic and mean arterial blood pressure variability. METHODS: All patients undergoing cardiac surgery from January 2008 to June 2014 were enrolled in this retrospective, single-center study. Demographic, intraoperative, and postoperative outcome data were obtained from the institution's Society of Thoracic Surgery database and Anesthesia Information Management System. Systolic and mean arterial blood pressure variability were assessed using the coefficient of variation (CV). The primary outcomes were 30-day mortality and in-hospital renal failure in relation to the entire duration of a case, while the secondary outcomes assessed phase-specific surgical periods. In an effort to control the family-wise error rate, P values <.0125 were considered significant for the primary outcomes. RESULTS: Of the 3687 patients analyzed, 2.7% of patients died within 30 days of surgery and 2.8% experienced in-hospital renal failure. After adjusting for significant covariates, we found a statistically significant association between increasing CV for systolic blood pressure (CVSBP) and 30-day mortality and in-hospital renal failure. For every 0.10 increase in CVSBP, there was a 150% increase in the odds of death (odds ratio, 2.50; 95% confidence interval, 1.60-3.92; P < .0001) and there was a 104% increase in odds of experiencing renal failure (odds ratio, 2.04; 95% confidence interval, 1.33-3.14; P = .001). The association with mortality was driven primarily by the prebypass period, because the association between CVSBP and mortality during the prebypass phase was significant (P = .01), and not during the postbypass phase (P = .08). There was no significant association between CV for mean arterial blood pressure and either death or renal failure during any period of surgery, including the bypass phase. CONCLUSIONS: Increasing systolic blood pressure variability was associated with 30-day mortality and development of renal failure, with surgery phase-specific relationships observed. Further research is required to determine how to prospectively detect blood pressure variability and elucidate opportunities for intervention.

An Embedded Device for Real-Time Noninvasive Intracranial Pressure Estimation.

OBJECTIVE: The monitoring of intracranial pressure (ICP) is indicated for diagnosing and guiding therapy in many neurological conditions. Current monitoring methods, however, are highly invasive, limiting their use to the most critically ill patients only. Our goal is to develop and test an embedded device that performs all necessary mathematical operations in real-time for noninvasive ICP (nICP) estimation based on a previously developed model-based approach that uses cerebral blood flow velocity (CBFV) and arterial blood pressure (ABP) waveforms. MATERIALS AND METHODS: The nICP estimation algorithm along with the required preprocessing steps were implemented on an NXP LPC4337 microcontroller unit (MCU). A prototype device using the MCU was also developed, complete with display, recording functionality, and peripheral interfaces for ABP and CBFV monitoring hardware. RESULTS: The device produces an estimate of mean ICP once per minute and performs the necessary computations in 410 ms, on average. Real-time nICP estimates differed from the original batch-mode MATLAB implementation of theestimation algorithm by 0.63 mmHg (root-mean-square error). CONCLUSIONS: We have demonstrated that real-time nICP estimation is possible on a microprocessor platform, which offers the advantages of low cost, small size, and product modularity over a general-purpose computer. These attributes take a step toward the goal of real-time nICP estimation at the patient's bedside in a variety of clinical settings.

A Waveform Archiving System for the GE Solar 8000i Bedside Monitor.

OBJECTIVES: Our objective was to develop, deploy, and test a data-acquisition system for the reliable and robust archiving of high-resolution physiological waveform data from a variety of bedside monitoring devices, including the GE Solar 8000i patient monitor, and for the logging of ancillary clinical and demographic information. MATERIALS AND METHODS: The data-acquisition system consists of a computer-based archiving unit and a GE Tram Rac 4A that connects to the GE Solar 8000i monitor. Standard physiological front-end sensors connect directly to the Tram Rac, which serves as a port replicator for the GE monitor and provides access to these waveform signals through an analog data interface. Together with the GE monitoring data streams, we simultaneously collect the cerebral blood flow velocity envelope from a transcranial Doppler ultrasound system and a non-invasive arterial blood pressure waveform along a common time axis. All waveform signals are digitized and archived through a LabView-controlled interface that also allows for the logging of relevant meta-data such as clinical and patient demographic information. RESULTS: The acquisition system was certified for hospital use by the clinical engineering team at Boston Medical Center, Boston, MA, USA. Over a 12-month period, we collected 57 datasets from 11 neuro-ICU patients. The system provided reliable and failure-free waveform archiving. We measured an average temporal drift between waveforms from different monitoring devices of 1 ms every 66 min of recorded data. CONCLUSIONS: The waveform acquisition system allows for robust real-time data acquisition, processing, and archiving of waveforms. The temporal drift between waveforms archived from different devices is entirely negligible, even for long-term recording.

Noninvasive Intracranial Pressure Determination in Patients with Subarachnoid Hemorrhage.

Intracranial pressure (ICP) should ideally be measured in many conditions affecting the brain. The invasiveness and associated risks of the measurement modalities in current clinical practice restrict ICP monitoring to a small subset of patients whose diagnosis and treatment could benefit from ICP measurement. To expand validation of a previously proposed model-based approach to continuous, noninvasive, calibration-free, and patient-specific estimation of ICP to patients with subarachnoid hemorrhage (SAH), we made waveform recordings of cerebral blood flow velocity in several major cerebral arteries during routine, clinically indicated transcranial Doppler examinations for vasospasm, along with time-locked waveform recordings of radial artery blood pressure (APB), and ICP was measured via an intraventricular drain catheter. We also recorded the locations to which ICP and ABP were calibrated, to account for a possible hydrostatic pressure difference between measured ABP and the ABP value at a major cerebral vessel. We analyzed 21 data records from five patients and were able to identify 28 data windows from the middle cerebral artery that were of sufficient data quality for the ICP estimation approach. Across these windows, we obtained a mean estimation error of -0.7 mmHg and a standard deviation of the error of 4.0 mmHg. Our estimates show a low bias and reduced variability compared with those we have reported before.

Open cranium model for the study of cerebrovascular dynamics in intracranial hypertension.

BACKGROUND: Significant research has been devoted to developing noninvasive approaches to neuromonitoring. Clinical validation of such approaches is often limited, with minimal data available in the clinically relevant elevated ICP range. NEW METHOD: To allow ultrasound-guided placement of an intraventricular catheter and to perform simultaneous long-duration ICP and ultrasound recordings of cerebral blood flow, we developed a large unilateral craniectomy in a swine model. We also used a microprocessor-controlled actuator for intraventricular saline infusion to reliably and reversibly manipulate ICP according to pre-determined profiles. RESULTS: The model was reproducible, resulting in over 80 hours of high-fidelity, multi-parameter physiological waveform recordings in twelve animals, with ICP ranging from 2 to 78 mmHg. ICP elevations were reversible and reproducible according to two predetermined profiles: a stepwise elevation up to an ICP of 30-35 mmHg and return to normotension, and a clinically significant plateau wave. Finally, ICP was elevated to extreme levels of greater than 60 mmHg, simulating extreme clinical emergency. COMPARISON WITH EXISTING METHODS: Existing methods for ICP monitoring in large animals typically relied on burr-hole approaches for catheter placement. Accurate catheter placement can be difficult in pigs, given the thickness of their skull. Additionally, ultrasound is significantly attenuated by the skull. The open cranium model overcomes these limitations. CONCLUSIONS: The hemicraniectomy model allowed for verified placement of the intraventricular catheter, and reversible and reliable ICP manipulation over a wide range. The large dural window additionally allowed for long-duration recording of cerebral blood flow velocity from the middle cerebral artery.

Dynamic Estimation of Cardiovascular State From Arterial Blood Pressure Recordings.

Real-time estimation of patient cardiovascular states, including cardiac output and systemic vascular resistance, is necessary for personalized hemodynamic monitoring and management. Highly invasive measurements enable reliable estimation of these states but increase patient risk. Prior methods using minimally invasive measurements reduce patient risk but have produced unreliable estimates limited due to trade-offs in accuracy and time resolution. Our objective was to develop an approach to estimate cardiac output and systemic vascular resistance with both a high time resolution and high accuracy from minimally invasive measurements. Using the two-element Windkessel model, we formulated a state-space method to estimate a dynamic time constant - the product of systemic vascular resistance and compliance - from arterial blood pressure measurements. From this time constant, we derived proportional estimates of systemic vascular resistance and cardiac output. We then validated our method with a swine cardiovascular dataset. Our estimates produced using arterial blood pressure measurements not only closely align with those using highly invasive measurements, but also closely align when derived from three separate locations on the arterial tree. Moreover, our estimates predictably change in response to standard cardiovascular drugs. Overall, our approach produces reliable, real-time estimates of cardiovascular states crucial for monitoring and control of the cardiovascular system.

A computational model of hemorrhage and dehydration suggests a pathophysiological mechanism: Starling-mediated protein trapping.

We sought to understand the degree to which a single computational cardiovascular model could replicate the typical responses of healthy subjects through a breadth of blood loss patterns and whether such a model could illuminate the cause-effect relationships that underlie the observed responses. The model consisted of compartments for the upper body, lower body, viscera, and kidneys as well as a four-chambered heart and a pulmonary compartment. Transcapillary fluid flux was governed by Starling forces, whereas lymphatic flow was driven by hydrostatic tissue pressure and scaled by a lymphatic activation term. We adjusted parameters based on results from one protocol involving moderate continual blood loss in a canine model. Next, we simulated six additional protocols spanning euvolemic and dehydrated subjects and compared in silico behavior with in vivo hemodynamic responses and fluid shifts. The model was able to replicate group-averaged behavior (i.e., within 1 or 2 SEs) of the rate and quantity of vascular refill and the associated cardiac output during slow, moderate, and rapid ongoing blood losses, the restitution after the cessation of blood loss, and the absence of restitution in dehydrated subjects. The model suggested that the earlier phase of restitution, i.e., transcapillary fluid shifts, was antagonistic to the later phase of restitution, i.e., protein return via lymphatics. This phenomenon was termed "interstitial protein trapping." In conclusion, the model appears valid for a range of blood loss patterns and prehydration states. Further investigation into the in vivo relevance of interstitial protein trapping is justified.

Low-Order Mechanistic Models for Volumetric and Temporal Capnography: Development, Validation, and Application.

OBJECTIVE: Develop low-order mechanistic models accounting quantitatively for, and identifiable from, the capnogram - the CO 2 concentration in exhaled breath, recorded over time (Tcap) or exhaled volume (Vcap). METHODS: The airflow model's single "alveolar" compartment has compliance and inertance, and feeds a resistive unperfused airway comprising a laminar-flow region followed by a turbulent-mixing region. The gas-mixing model tracks mixing-region CO 2 concentration, fitted breath-by-breath to the measured capnogram, yielding estimates of model parameters that characterize the capnogram. RESULTS: For the 17 examined records (310 breaths) of airflow, airway pressure and Tcap from ventilated adult patients, the models fit closely (mean rmse 1% of end-tidal CO 2 concentration on Vcap; 1.7% on Tcap). The associated parameters (4 for Vcap, 5 for Tcap) for each exhalation, and airflow parameters for the corresponding forced inhalation, are robustly estimated, and consonant with literature values. The models also allow, using Tcap alone, estimation of the entire exhaled airflow waveform to within a scaling. This suggests new Tcap-based tests, analogous to spirometry but with normal breathing, for discriminating chronic obstructive pulmonary disease (COPD) from congestive heart failure (CHF). A version trained on 15 exhalations from each of 24 COPD/24 CHF Tcap records from one hospital, then tested 100 times with 15 random exhalations from each of 27 COPD/31 CHF Tcap records at another, gave mean accuracy 80.6% (stdev 2.1%). Another version, tested on 29 COPD/32 CHF, yielded AUROC 0.84. CONCLUSION: Our mechanistic models closely fit Tcap and Vcap measurements, and yield subject-specific parameter estimates. SIGNIFICANCE: This can inform cardiorespiratory care.

Fatigue Assessment from Facial Videos using Deep Neural Networks and Engineered Features Informed by Domain Knowledge.

Fatigue impairs cognitive and motor function, potentially leading to mishaps in high-pressure occupations such as aviation and emergency medical services. The current approach is primarily based on self-assessment, which is subjective and error-prone. An objective method is needed to detect severe and likely dangerous levels of fatigue quickly and accurately. Here, we present a quantitative evaluation tool that uses less than two minutes of facial video, captured using an iPad, to assess fatigue vs. alertness. The tool is fast, easy to use, and scalable since it uses cameras readily available on consumer-electronic devices. We compared the classification performance between a Long Short-Term Memory (LSTM) deep neural network and a Random Forest (RF) classifier applied to engineered features informed by domain knowledge. The preliminary results on an 11-subject dataset show that RF outperforms LSTM, with added interpretability on the features used. For the RF classifiers, the average areas under the receiver operating characteristic curve, based on the 11-fold and individualized 11-fold cross validations, are 0.72 ± 0.16 and 0.8 ± 0.12, respectively. Equal error rates are 0.34 and 0.26, respectively. This study presents a promising approach for rapid fatigue detection. Additional data will be collected to assess the generalizability across populations.

Diagnostic suspicion bias and machine learning: Breaking the awareness deadlock for sepsis detection.

Many early warning algorithms are downstream of clinical evaluation and diagnostic testing, which means that they may not be useful when clinicians fail to suspect illness and fail to order appropriate tests. Depending on how such algorithms handle missing data, they could even indicate "low risk" simply because the testing data were never ordered. We considered predictive methodologies to identify sepsis at triage, before diagnostic tests are ordered, in a busy Emergency Department (ED). One algorithm used "bland clinical data" (data available at triage for nearly every patient). The second algorithm added three yes/no questions to be answered after the triage interview. Retrospectively, we studied adult patients from a single ED between 2014-16, separated into training (70%) and testing (30%) cohorts, and a final validation cohort of patients from four EDs between 2016-2018. Sepsis was defined per the Rhee criteria. Investigational predictors were demographics and triage vital signs (downloaded from the hospital EMR); past medical history; and the auxiliary queries (answered by chart reviewers who were blinded to all data except the triage note and initial HPI). We developed L2-regularized logistic regression models using a greedy forward feature selection. There were 1164, 499, and 784 patients in the training, testing, and validation cohorts, respectively. The bland clinical data model yielded ROC AUC's 0.78 (0.76-0.81) and 0.77 (0.73-0.81), for training and testing, respectively, and ranged from 0.74-0.79 in four hospital validation. The second model which included auxiliary queries yielded 0.84 (0.82-0.87) and 0.83 (0.79-0.86), and ranged from 0.78-0.83 in four hospital validation. The first algorithm did not require clinician input but yielded middling performance. The second showed a trend towards superior performance, though required additional user effort. These methods are alternatives to predictive algorithms downstream of clinical evaluation and diagnostic testing. For hospital early warning algorithms, consideration should be given to bias and usability of various methods.

Continuous quantitative monitoring of cerebral oxygen metabolism in neonates by ventilator-gated analysis of NIRS recordings.

Oxidative stress during fetal development, delivery, or early postnatal life is a major cause of neuropathology, as both hypoxic and hyperoxic insults can significantly damage the developing brain. Despite the obvious need for reliable cerebral oxygenation monitoring, no technology currently exists to monitor cerebral oxygen metabolism continuously and noninvasively in infants at high risk for developing brain injury. Consequently, a rational approach to titrating oxygen supply to cerebral oxygen demand - and thus avoiding hyperoxic or hypoxic insults - is currently lacking. We present a promising method to close this crucial technology gap in the important case of neonates on conventional ventilators. By using cerebral near-infrared spectroscopy and signals from conventional ventilators, along with arterial oxygen saturation, we derive continuous (breath-by-breath) estimates of cerebral venous oxygen saturation, cerebral oxygen extraction fraction, cerebral blood flow, and cerebral metabolic rate of oxygen. The resultant estimates compare very favorably to previously reported data obtained by non-continuous and invasive means from preterm infants in neonatal critical care.

Deconvolution-Based Partial Volume Correction for Volumetric Blood Flow Measurement.

Ultrasound-based blood flow (BF) monitoring is vital in the diagnosis and treatment of a variety of cardiovascular and neurologic conditions. Finite spatial resolution of clinical color flow (CF) systems, however, has hampered measurement of vessel cross Section areas. We propose a resolution enhancement technique that allows reliable determination of BF in small vessels. We leverage sparsity in the spatial distribution of the frequency spectrum of routinely collected CF data to blindly determine the point spread function (PSF) of the imaging system in a robust manner. The CF data are then deconvolved with the PSF, and the volumetric flow is computed using the resulting velocity profiles. Data were collected from phantom blood vessels with diameters between 2 and 6 mm using a clinical ultrasound system at 2 MHz insonation frequency. The proposed method yielded a flow estimation bias of 0 mL/min, standard deviation of error (SDE) of 22 mL/min, and a root-mean-square error (RMSE) of 22 mL/min over a 150 mL/min range of mean flows. Recordings were also obtained in low signal-to-noise ratio (SNR) conditions using a skull mimicking element, resulting in an estimation bias of -13 mL/min, SDE of 23 mL/min, and an RMSE of 26 mL/min. The effect of insonation frequency was also investigated by obtaining recordings at 4.3 MHz, yielding an estimation bias of -16 mL/min, SDE of 16 mL/min, and an RMSE of 22 mL/min. The results indicate that our technique can lead to clinically acceptable flow measurements across a range of vessel diameters in high and low SNR regimes.

Modeling of Usual Care: Vasopressor Initiation for Sepsis With Hypotension.

Usual care regarding vasopressor initiation is ill-defined. We aimed to develop a quantitative "dynamic practice" model for usual care in the emergency department (ED) regarding the timing of vasopressor initiation in sepsis. In a retrospective study of 589 septic patients with hypotension in an urban tertiary care center ED, we developed a multi-variable model that distinguishes between patients who did and did not subsequently receive sustained (>24 h) vasopressor therapy. Candidate predictors were vital signs, intravenous fluid (IVF) volumes, laboratory measurements, and elapsed time from triage computed at timepoints leading up to the final decision timepoint of either vasopressor initiation or ED hypotension resolution without vasopressors. A model with six independently significant covariates (respiratory rate, Glasgow Coma Scale score, SBP, SpO2, administered IVF, and elapsed time) achieved a C-statistic of 0.78 in a held-out test set at the final decision timepoint, demonstrating the ability to reliably model usual care for vasopressor initiation for hypotensive septic patients. The included variables measured depth of hypotension, extent of disease severity and organ dysfunction. At an operating point of 90% specificity, the model identified a minority of patients (39%) more than an hour before actual vasopressor initiation, during which time a median of 2,250 (IQR 1,200-3,300) mL of IVF was administered. This single-center analysis shows the feasibility of a quantitative, objective tool for describing usual care. Dynamic practice models may help assess when management was atypical; such tools may also be useful for designing and interpreting clinical trials.