The efficacy of novel anatomical sites for the assessment of muscle oxygenation during central hypovolemia.

Muscle tissue oxygenation (SmO2) can track central blood volume loss associated with hemorrhage. Traditional peripheral measurement sites (e.g., forearm) may not be practical due to excessive movement or injury (e.g., amputation). The aim of this study was to evaluate the efficacy of three novel anatomical sites for the assessment of SmO2 under progressive central hypovolemia. 10 male volunteers were exposed to stepwise prone lower body negative pressure to decrease central blood volume, while SmO2 was assessed at four sites-the traditional site of the flexor carpi ulnaris (ARM), and three novel sites not previously investigated during lower body negative pressure, the deltoid, latissimus dorsi, and trapezius. SmO2 at the novel sites was compared to the ARM sensor and to stroke volume responses. A reduction in SmO2 was detected by the ARM sensor at the first level of lower body negative pressure (-15 mmHg; P = 0.007), and at -30 (the deltoid), -45 (latissimus dorsi), and -60 mmHg lower body negative pressure (trapezius) at the novel sites (P ≤ 0.04). SmO2 responses at all novel sites were correlated with responses at the ARM (R ≥ 0.89), and tracked the reduction in stroke volume (R ≥ 0.87); the latissimus dorsi site exhibited the strongest linear correlations (R ≥ 0.96). Of the novel sensor sites, the latissimus dorsi exhibited the strongest linear associations with SmO2 at the ARM, and with reductions in central blood volume. These findings have important implications for detection of hemorrhage in austere environments (e.g., combat) when use of a peripheral sensor may not be ideal, and may facilitate incorporation of these sensors into uniforms.

Multi-parameter vital sign database to assist in alarm optimization for general care units.

Continual vital sign assessment on the general care, medical-surgical floor is expected to provide early indication of patient deterioration and increase the effectiveness of rapid response teams. However, there is concern that continual, multi-parameter vital sign monitoring will produce alarm fatigue. The objective of this study was the development of a methodology to help care teams optimize alarm settings. An on-body wireless monitoring system was used to continually assess heart rate, respiratory rate, SpO2 and noninvasive blood pressure in the general ward of ten hospitals between April 1, 2014 and January 19, 2015. These data, 94,575 h for 3430 patients are contained in a large database, accessible with cloud computing tools. Simulation scenarios assessed the total alarm rate as a function of threshold and annunciation delay (s). The total alarm rate of ten alarms/patient/day predicted from the cloud-hosted database was the same as the total alarm rate for a 10 day evaluation (1550 h for 36 patients) in an independent hospital. Plots of vital sign distributions in the cloud-hosted database were similar to other large databases published by different authors. The cloud-hosted database can be used to run simulations for various alarm thresholds and annunciation delays to predict the total alarm burden experienced by nursing staff. This methodology might, in the future, be used to help reduce alarm fatigue without sacrificing the ability to continually monitor all vital signs.

Comparison of Noninvasive pH and Blood Lactate as Predictors of Mortality in a Swine Hemorrhagic Shock with Restricted Volume Resuscitation Model.

Recent clinical studies have demonstrated that high blood lactate in the prehospital setting and poor lactate clearance in the emergency department are predictive of in-hospital mortality. This analysis of data collected from a swine model of hemorrhage and restricted volume resuscitation investigated the hypotheses that noninvasive muscle pH (pHm) and H clearance would predict mortality, and the responses would be similar between pHm and lactate. Data from a set of 57 swine were analyzed over the first 2 h after controlled hemorrhage and uncontrolled splenic bleeding. Surviving animals were ones that lived for the full 5-h experimental period. Venous lactate was determined at baseline, shock, and at 30, 60, and 120 min after injury. Spectra were collected continuously from the posterior thigh using a prototype CareGuide 1100 Oximeter and pHm calculated from the spectra; H concentration was determined from pHm. Lactate clearance rate was calculated from the difference in lactate concentration at 120 min and shock, and H clearance was calculated in a similar manner. Comparison of the area under the receiver operator characteristic curves was used to assess prediction of survival at 5 h after injury. At 120 min after injury, lactate, lactate clearance, noninvasive pHm, and noninvasive H clearance were equivalent predictors of mortality each with a receiver operator characteristic area under the curve of 0.87. Thresholds for single lactate (<3.8 mmol/L) or pHm (>7.30) determinations were found to be consistent with a resuscitation goal targeted to reverse acidosis. Continuous, noninvasive pHm monitoring may provide a substitute for lactate measurement in trauma patients, particularly in the prehospital and emergency department settings.

Tissue oxygen saturation during hyperthermic progressive central hypovolemia.

During normothermia, a reduction in near-infrared spectroscopy (NIRS)-derived tissue oxygen saturation (So2) is an indicator of central hypovolemia. Hyperthermia increases skin blood flow and reduces tolerance to central hypovolemia, both of which may alter the interpretation of tissue So2 during central hypovolemia. This study tested the hypothesis that maximal reductions in tissue So2 would be similar throughout normothermic and hyperthermic central hypovolemia to presyncope. Ten healthy males (means ± SD; 32 ± 5 yr) underwent central hypovolemia via progressive lower-body negative pressure (LBNP) to presyncope during normothermia (skin temperature ≈34°C) and hyperthermia (+1.2 ± 0.1°C increase in internal temperature via a water-perfused suit, skin temperature ≈39°C). NIRS-derived forearm (flexor digitorum profundus) tissue So2 was measured throughout and analyzed as the absolute change from pre-LBNP. Hyperthermia reduced (P < 0.001) LBNP tolerance by 49 ± 33% (from 16.7 ± 7.9 to 7.2 ± 3.9 min). Pre-LBNP, tissue So2 was similar (P = 0.654) between normothermia (74 ± 5%) and hyperthermia (73 ± 7%). Tissue So2 decreased (P < 0.001) throughout LBNP, but the reduction from pre-LBNP to presyncope was greater during normothermia (-10 ± 6%) than during hyperthermia (-6 ± 5%; P = 0.041). Contrary to our hypothesis, these findings indicate that hyperthermia is associated with a smaller maximal reduction in tissue So2 during central hypovolemia to presyncope.

Preliminary evaluation of near infrared spectroscopy as a method to detect plasma leakage in children with dengue hemorrhagic fever.

BACKGROUND: Dengue viral infections are prevalent in the tropical and sub-tropical regions of the world, resulting in substantial morbidity and mortality. Clinical manifestations range from a self-limited fever to a potential life-threatening plasma leakage syndrome (dengue hemorrhagic fever). The objective of this study was to assess the utility of near infrared spectroscopy (NIRS) measurements of muscle oxygen saturation (SmO2) as a possible continuous measure to detect plasma leakage in children with dengue. METHODS: Children ages 6 months to 15 years of age admitted with suspected dengue were enrolled from the dengue ward at Queen Sirikit National Institute for Child Health. Children were monitored daily until discharge. NIRS data were collected continuously using a prototype CareGuide Oximeter 1100 with sensors placed on the deltoid or thigh. Daily ultrasound of the chest and a right lateral decubitus chest x-ray the day after defervescence were performed to detect and quantitate plasma leakage in the pleural cavity. RESULTS: NIRS data were obtained from 19 children with laboratory-confirmed dengue. Average minimum SmO2 decreased for all subjects prior to defervescence. Average minimum SmO2 subsequently increased in children with no ultrasound evidence of pleural effusion but remained low in children with pleural effusion following defervescence. Average minimum SmO2 was inversely correlated with pleural space fluid volume. ROC analysis revealed a cut-off value for SmO2 which yielded high specificity and sensitivity. CONCLUSIONS: SmO2 measured using NIRS may be a useful guide for real-time and non-invasive identification of plasma leakage in children with dengue. Further investigation of the utility of NIRS measurements for prediction and management of severe dengue syndromes is warranted.

Investigation of noninvasive muscle pH and oxygen saturation during uncontrolled hemorrhage and resuscitation in swine.

This study evaluated noninvasively determined muscle pH (pHm) and muscle oxygen saturation (SmO2) in a swine shock model that used uncontrolled hemorrhage and restricted volume resuscitation. Anesthetized 40-kg female swine underwent hemorrhage until 24 mL/kg of blood was removed (n = 26), followed by transection of the spleen, causing uncontrolled hemorrhage throughout the remainder of the protocol. After 15 min, 15 mL/kg of resuscitation fluid (Hextend, fresh-frozen plasma or platelets) was given for 30 min. Arterial and venous blood gases were measured at baseline, shock, end of resuscitation, and end of the study (death or 5 h), along with lactate and base excess. In addition, seven animals underwent a sham procedure. Spectra were collected continuously from the posterior thigh using a prototype CareGuide 1100 Oximeter, and pHm and SmO2 were calculated from the spectra. A two-factor analysis of variance with repeated measures followed by Tukey post hoc comparisons was used to compare experimental factors. It was shown that, for both pH and SO2, venous and muscle values were similar to each other at the end of the resuscitation period and at the end of the study for both surviving and nonsurviving animals. pH and SO2, venous and muscle, significantly declined as a result of bleeding, but lactate and base excess did not show significant changes during this period. Noninvasive pHm and SmO2 tracked the adequacy of resuscitation in real time, indicating at the time all of the fluid was delivered, which animals would live and which would die. The results of this swine study indicate that further evaluation on trauma patients is warranted.

Lightweight noninvasive trauma monitor for early indication of central hypovolemia and tissue acidosis: a review.

BACKGROUND: Hemorrhage is a major cause of soldier death; it must be quickly identified and appropriately treated. We developed a prototype patient monitor that noninvasively and continuously determines muscle oxygen saturation (SmO2), muscle pH (pHm), and a regional assessment of blood volume (HbT) using near-infrared spectroscopy. Previous demonstration in a model of progressive, central hypovolemia induced by lower body negative pressure (LBNP) showed that SmO2 provided an early indication of impending hemodynamic instability in humans. In this review, we expand the number of subjects and provide an overview of the relationship between the muscle and sublingual microcirculation in this model of compensated shock. METHODS: Healthy human volunteers (n = 30) underwent progressive LBNP in 5-minute intervals. Standard vital signs, along with stroke volume (SV), total peripheral resistance, functional capillary density, SmO2, HbT, and pHm were measured continuously throughout the study. RESULTS AND DISCUSSION: SmO2 and SV significantly decreased during the first level of central hypovolemia (-15 mm Hg LBNP), whereas vital signs were later indicators of impending cardiovascular collapse. SmO2 declined with SV and inversely with total peripheral resistance throughout LBNP. HbT was correlated with declining functional capillary density, suggesting vasoconstriction as a cause for decreased SmO2 and subsequently decreased pHm. CLINICAL TRANSLATION: The monitor has been miniaturized to a 58-g solid-state sensor that is currently being evaluated on patients with dengue hemorrhagic fever. Early results demonstrate significant decreases in SmO2 similar to those observed with progressive reductions in central blood volume. As such, this technology has the potential to (1) provide a monitoring capability for both nontraumatic and traumatic hemorrhage and (2) help combat medics triage casualties and monitor patients during lengthy transport from combat areas.

Near infrared spectroscopy-derived interstitial hydrogen ion concentration and tissue oxygen saturation during ambulation.

The objective of this study was to determine whether walking and running at different treadmill speeds resulted in different metabolic and cardiovascular responses in the vastus lateralis (VL) and lateral gastrocnemius (LG) by examining metabolite accumulation and tissue oxygen saturation. Ten healthy subjects (6 males, 4 females) completed a submaximal treadmill exercise test, beginning at 3.2 km h(-1) and increasing by 1.6 km h(-1) increments every 3 min until reaching 85% of age-predicted maximal heart rate. Muscle tissue oxygenation (SO(2)), total hemoglobin (HbT) and interstitial hydrogen ion concentration ([H(+)]) were calculated from near infrared spectra collected from VL and LG. The [H(+)] threshold for each muscle was determined using a simultaneous bilinear regression. Muscle and treadmill speed effects were analyzed using a linear mixed model analysis. Paired t-tests were used to test for differences between muscles in the [H(+)] threshold. SO(2) decreased (P = 0.001) during running in the VL and LG, but the SO(2) response across treadmill speeds was different between muscles (P = 0.047). In both muscles, HbT and [H(+)] increased as treadmill speed increased (P < 0.001), but the response to exercise was not different between muscles. The [H(+)] threshold occurred at a lower whole-body VO(2) in the LG (1.22 ± 0.63 L min(-1)) than in the VL (1.46 ± 0.58 L min(-1), P = 0.01). In conclusion, interstitial [H(+)] and SO(2) are aggregate measures of local metabolite production and the cardiovascular response. Inferred from simultaneous SO(2) and [H(+)] measures in the VL and LG muscles, muscle perfusion is well matched to VL and LG work during walking, but not running.

Oxygen transport characterization of a human model of progressive hemorrhage.

BACKGROUND: Hemorrhage continues to be a leading cause of death from trauma sustained both in combat and in the civilian setting. New models of hemorrhage may add value in both improving our understanding of the physiologic responses to severe bleeding and as platforms to develop and test new monitoring and therapeutic techniques. We examined changes in oxygen transport produced by central volume redistribution in humans using lower body negative pressure (LBNP) as a potential mimetic of hemorrhage. METHODS AND RESULTS: In 20 healthy volunteers, systemic oxygen delivery and oxygen consumption, skeletal muscle oxygenation and oral mucosa perfusion were measured over increasing levels of LBNP to the point of hemodynamic decompensation. With sequential reductions in central blood volume, progressive reductions in oxygen delivery and tissue oxygenation and perfusion parameters were noted, while no changes were observed in systemic oxygen uptake or markers of anaerobic metabolism in the blood (e.g., lactate, base excess). While blood pressure decreased and heart rate increased during LBNP, these changes occurred later than the reductions in tissue oxygenation and perfusion. CONCLUSIONS: These findings indicate that LBNP induces changes in oxygen transport consistent with the compensatory phase of hemorrhage, but that a frank state of shock (delivery-dependent oxygen consumption) does not occur. LBNP may therefore serve as a model to better understand a variety of compensatory physiological changes that occur during the pre-shock phase of hemorrhage in conscious humans. As such, LBNP may be a useful platform from which to develop and test new monitoring capabilities for identifying the need for intervention during the early phases of hemorrhage to prevent a patient's progression to overt shock.

Investigation of spectral interferences on the accuracy of broadband CW-NIRS tissue SO(2) determination.

An accurate SO(2) prediction method for using broadband continuous-wave diffuse reflectance near infrared (NIR) spectroscopy is proposed. The method fitted the NIR spectra to a Taylor expansion attenuation model, and used the simulated annealing method to initialize the nonlinear least squares fit. This paper investigated the effect of potential spectral interferences that are likely to be encountered in clinical use, on SO(2) prediction accuracy. The factors include the concentration of hemoglobin in blood, the volume of blood and volume of water in the tissue under the sensor, reduced scattering coefficient, µ(s)', of the muscle, fat thickness and the source-detector spacing. The SO(2) prediction method was evaluated on simulated muscle spectra as well as on dual-dye phantoms which simulate the absorbance of oxygenated and deoxygenated hemoglobin.

Noninvasively determined muscle oxygen saturation is an early indicator of central hypovolemia in humans.

Ten healthy human volunteers were subjected to progressive lower body negative pressure (LBNP) to the onset of cardiovascular collapse to compare the response of noninvasively determined skin and fat corrected deep muscle oxygen saturation (SmO2) and pH to standard hemodynamic parameters for early detection of imminent hemodynamic instability. Muscle SmO2 and pH were determined with a novel near infrared spectroscopic (NIRS) technique. Heart rate (HR) was measured continuously via ECG, and arterial blood pressure (BP) and stroke volume (SV) were obtained noninvasively via Finometer and impedance cardiography on a beat-to-beat basis. SmO2 and SV were significantly decreased during the first LBNP level (-15 mmHg), whereas HR and BP were late indicators of impending cardiovascular collapse. SmO2 declined in parallel with SV and inversely with total peripheral resistance, suggesting, in this model, that SmO2 is an early indicator of a reduction in oxygen delivery through vasoconstriction. Muscle pH decreased later, suggesting an imbalance between delivery and demand. Spectroscopic determination of SmO2 is noninvasive and continuous, providing an early indication of impending cardiovascular collapse resulting from progressive reduction in central blood volume.

Noninvasive determination of exercise-induced hydrodgen ion threshold through direct optical measurement.

The intensity of exercise above which oxygen uptake (Vo2) does not account for all of the required energy to perform work has been associated with lactate accumulation in the blood (lactate threshold, LT) and elevated carbon dioxide output (gas exchange threshold). An increase in hydrogen ion concentration ([H+]) is approximately concurrent with elevation of blood lactate and CO2 output during exercise. Near-infrared spectra (NIRS) and invasive interstitial fluid pH (pHm) were measured in the flexor digitorum profundus during handgrip exercise to produce a mathematical model relating the two measures with an estimated error of 0.035 pH units. This NIRS pHm model was subsequently applied to spectra collected from the vastus lateralis of 10 subjects performing an incremental-intensity cycle protocol. Muscle oxygen saturation (SmO2) was also calculated from spectra. We hypothesized that a H+ threshold could be identified for these subjects and that it would be different from but correlated with the LT. Lactate, gas exchange, SmO2, and H+ thresholds were determined as a function of Vo2 using bilinear regression. LT was significantly different from both the gas exchange threshold (Delta = 0.27 +/- 0.29 l/min) and H+ threshold (Delta = 0.29 +/- 0.23 l/min), but the gas exchange threshold was not significantly different from the H+ threshold (Delta = 0.00 +/- 0.38 l/min). The H+ threshold was strongly correlated with LT (R2 = 0.95) and the gas exchange threshold (R2 = 0.85). This initial study demonstrates the feasibility of noninvasive pHm estimations, the determination of H+ threshold, and the relationship between H+ and classical metabolic thresholds during incremental exercise.

Oxygen saturation determined from deep muscle, not thenar tissue, is an early indicator of central hypovolemia in humans.

OBJECTIVE: To compare the responses of noninvasively measured tissue oxygen saturation (StO2) and calculated muscle oxygen tension (PmO2) to standard hemodynamic variables for early detection of imminent hemodynamic instability during progressive central hypovolemia in humans. DESIGN: Prospective study. SETTING: Research laboratory. SUBJECTS: Sixteen healthy human volunteers. INTERVENTIONS: Progressive lower body negative pressure (LBNP) to onset of cardiovascular collapse. MEASUREMENTS AND MAIN RESULTS: Noninvasive measurements of blood pressures, heart rate, and stroke volume were obtained during progressive LBNP with simultaneous assessments of StO2, PmO2, and muscle oxygen saturation (SmO2). Forearm SmO2 and PmO2 were determined with a novel near infrared spectroscopic measurement device (UMMS) and compared with thenar StO2 measured by a commercial device (HT). All values were normalized to the duration of LBNP exposure required for cardiovascular collapse in each subject (i.e., LBNP maximum). Stroke volume was significantly decreased at 25% of LBNP maximum, whereas blood pressure was a late indicator of imminent cardiovascular collapse. PmO2 (UMMS) was significantly decreased at 50% of maximum LBNP while SmO2 (UMMS) decreased at 75% of maximum LBNP. Thenar StO2 (HT) showed no statistical change throughout the entire LBNP protocol. CONCLUSIONS: Spectroscopic assessment of forearm muscle PO2 and SmO2 provides noninvasive and continuous measures that are early indicators of impending cardiovascular collapse resulting from progressive reductions in central blood volume.

Comparison of intramuscular and venous blood pH, PCO(2) and PO(2) during rhythmic handgrip exercise.

Oxygen and acid-base status during exercise is well established for the lungs, large arteries and veins. However, values for these parameters in exercising muscle are less frequently reported. In this study we examined the relationship between intramuscular PO(2), pH, PCO(2) and the comparable venous values during rhythmic isometric handgrip exercise at target levels of 15%, 30% and 45% of maximum voluntary contraction (MVC). A small fiber optic sensor was inserted into the flexor digitorum profundus (FDP) muscle for continuous measurement of intramuscular (IM) PO(2), pH and PCO(2). Venous blood samples were taken from the forearm every minute during each exercise bout. IM pH and PCO(2) were similar to their venous counterparts at baseline, but the difference between IM and venous values increased when exercise exceeded 30% MVC. During exercise at 15% MVC and greater, venous PO(2) declined from 40 to 21 Torr (approximately 5.3 to 2.8 kPa). IM PO(2) declined from 24 to 8 Torr with 15% MVC, and approached 0 Torr at 30% MVC and 45% MVC. IM pH declined rapidly when IM PO(2) reached 10 Torr and continued to decrease with increasing exertion, despite an IM PO(2) near 0 Torr.

Noninvasive in vivo measurement of venous blood pH during exercise using near-infrared reflectance spectroscopy.

Blood pH is an important indicator of anaerobic metabolism in exercising muscle. This paper demonstrates multivariate calibration techniques that can be used to produce a general pH model that can be applied to spectra from any new subject without significant prediction error. Tissue spectra (725 approximately 880 nm) were acquired through the skin overlying the flexor digitorum profundus muscle on the forearms of eight healthy subjects during repetitive hand-grip exercise and referenced to the pH of venous blood drawn from a catheter placed in a vein close to the muscle. Calibration models were developed using multi-subject partial least squares (PLS) and validated using subject-out cross-validation after the subject-to-subject spectral variations were corrected by mathematical preprocessing methods. A combination of standard normal variate (SNV) scaling and principal component analysis loading correction (PCALC) successfully removed most of the subject-to-subject variations and provided the most accurate prediction results.

Quantitative measurement of muscle oxygen saturation without influence from skin and fat using continuous-wave near infrared spectroscopy.

A method to non-invasively and quantitatively measure muscle oxygen saturation (SmO(2)) using broadband continuous-wave diffuse reflectance near infrared (NIR) spectroscopy is presented. The method obtained SmO(2) by first correcting NIR spectra for absorption and scattering of skin pigment and fat, then fitting to a Taylor expansion attenuation model. A non-linear least squares optimization algorithm with set boundary constraints on the fitting parameters was used to fit the model to the acquired spectra. A data preprocessing/optimization scheme for accurately determining the initial values needed for the optimization was also employed. The method was evaluated on simulated muscle spectra with 4 different scattering properties, as well as on in vivo forearm spectra from 5 healthy volunteer subjects during arterial occlusion. Measurement repeatability was assessed on 24 healthy volunteers with 5 repeated measurements, each separated by at least 48 hours.

Removal of analyte-irrelevant variations in near-infrared tissue spectra.

This paper describes mathematical techniques to correct for analyte-irrelevant optical variability in tissue spectra by combining multiple preprocessing techniques to address variability in spectral properties of tissue overlying and within the muscle. A mathematical preprocessing method called principal component analysis (PCA) loading correction is discussed for removal of inter-subject, analyte-irrelevant variations in muscle scattering from continuous-wave diffuse reflectance near-infrared (NIR) spectra. The correction is completed by orthogonalizing spectra to a set of loading vectors of the principal components obtained from principal component analysis of spectra with the same analyte value, across different subjects in the calibration set. Once the loading vectors are obtained, no knowledge of analyte values is required for future spectral correction. The method was tested on tissue-like, three-layer phantoms using partial least squares (PLS) regression to predict the absorber concentration in the phantom muscle layer from the NIR spectra. Two other mathematical methods, short-distance correction to remove spectral interference from skin and fat layers and standard normal variate scaling, were also applied and/or combined with the proposed method prior to the PLS analysis. Each of the preprocessing methods improved model prediction and/or reduced model complexity. The combination of the three preprocessing methods provided the most accurate prediction results. We also performed a preliminary validation on in vivo human tissue spectra.

Simultaneous correction of the influence of skin color and fat on tissue spectroscopy by use of a two-distance fiber-optic probe and orthogonalization technique.

We have demonstrated simultaneous correction for the optical interference of skin and fat in tissue spectra by using a two-distance fiber-optic probe. We obtained the correction by orthogonalizing the spectra collected at a long source-detector distance (SD) to the spectra collected at a short SD and mapped to the long SD space. The method was validated in tissuelike three-layer phantoms as well as preliminarily in human tissue. After the correction, a partial-least-squares model of the phantoms showed enhanced prediction performance.

Influence of a fat layer on the near infrared spectra of human muscle: quantitative analysis based on two-layered Monte Carlo simulations and phantom experiments.

The influence of fat thickness on the diffuse reflectance spectra of muscle in the near infrared (NIR) region is studied by Monte Carlo simulations of a two-layer structure and with phantom experiments. A polynomial relationship was established between the fat thickness and the detected diffuse reflectance. The influence of a range of optical coefficients (absorption and reduced scattering) for fat and muscle over the known range of human physiological values was also investigated. Subject-to-subject variation in the fat optical coefficients and thickness can be ignored if the fat thickness is less than 5 mm. A method was proposed to correct the fat thickness influence.