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Noninvasive Cellular Oxygenation Measurement During Graded Hypoxia Using Visible–Near-Infrared Spectroscopy
Abstract
In critically ill patients, direct knowledge of intracellular pO 2 would allow for identification of cellular hypoxia, which when prolonged leads to organ failure. We have developed a visible–near-infrared optical system that noninvasively measures myoglobin saturation, which is directly related to intracellular pO 2 , from the surface of the skin. We used an animal model of graded hypoxia from low levels of inspired oxygen ( n = 5) and verified that low intracellular pO 2 is correlated with high steady-state serum lactate values. In addition, the pO 2 gradient between arterial blood and inside muscle cells was 83 mm Hg at 21% O 2 , but fell to 24 mm Hg at 8% O 2 . Continuous myoglobin saturation measurement in skeletal muscle displayed the same trends as cerebral oxygenation with no lag in changes over time, demonstrating its relevance as a measure of systemic oxygenation.
Objectives
This study aims to demonstrate the potential of myoglobin saturation as an indicator of oxygen delivery adequacy to help determine the need for red cell transfusion.
Background
Modern blood management approaches have been established to optimise use of red blood cells for transfusions in patients with anaemia. However, most approaches make recommendations to transfuse based on haemoglobin or haematocrit levels and do not directly address adequacy of oxygen delivery. Intracellular oxygen determined by myoglobin saturation directly measures oxygen delivery at the tissue level.
Methods/Materials
A custom built spectrometer system with an optical fibre probe was used in this pilot study to measure muscle cell myoglobin saturation noninvasively from the first digital interosseous muscles in patients undergoing planned red blood cell transfusion. Patients were recruited from both the in‐patient and out‐patient oncology service at a major university medical centre. Measurements were made immediately before, immediately after, and 24 h following transfusion. Clinical data and tissue oxygen values from the Somanetics INVOS system were also collected.
Results
Myoglobin saturation, and thus cellular oxygen increased in some, but not all patients receiving a transfusion, and was most pronounced in patients who initially had low myoglobin saturation compared with the group as a whole.
Conclusion
Clinical decisions to transfuse based on haemoglobin or haematocrit thresholds alone are likely insufficient to optimise use of red blood cell transfusions. The combination of haemoglobin or haematocrit with myoglobin saturation may optimally determine who will benefit physiologically from a transfusion.
Importance
Estimates from claims-based analyses suggest that the incidence of sepsis is increasing and mortality rates from sepsis are decreasing. However, estimates from claims data may lack clinical fidelity and can be affected by changing diagnosis and coding practices over time.
Objective
To estimate the US national incidence of sepsis and trends using detailed clinical data from the electronic health record (EHR) systems of diverse hospitals.
Design, Setting, and Population
Retrospective cohort study of adult patients admitted to 409 academic, community, and federal hospitals from 2009-2014.
Exposures
Sepsis was identified using clinical indicators of presumed infection and concurrent acute organ dysfunction, adapting Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria for objective and consistent EHR-based surveillance.
Main Outcomes and Measures
Sepsis incidence, outcomes, and trends from 2009-2014 were calculated using regression models and compared with claims-based estimates using International Classification of Diseases, Ninth Revision, Clinical Modification codes for severe sepsis or septic shock. Case-finding criteria were validated against Sepsis-3 criteria using medical record reviews.
Results
A total of 173 690 sepsis cases (mean age, 66.5 [SD, 15.5] y; 77 660 [42.4%] women) were identified using clinical criteria among 2 901 019 adults admitted to study hospitals in 2014 (6.0% incidence). Of these, 26 061 (15.0%) died in the hospital and 10 731 (6.2%) were discharged to hospice. From 2009-2014, sepsis incidence using clinical criteria was stable (+0.6% relative change/y [95% CI, −2.3% to 3.5%], P = .67) whereas incidence per claims increased (+10.3%/y [95% CI, 7.2% to 13.3%], P < .001). In-hospital mortality using clinical criteria declined (−3.3%/y [95% CI, −5.6% to −1.0%], P = .004), but there was no significant change in the combined outcome of death or discharge to hospice (−1.3%/y [95% CI, −3.2% to 0.6%], P = .19). In contrast, mortality using claims declined significantly (−7.0%/y [95% CI, −8.8% to −5.2%], P < .001), as did death or discharge to hospice (−4.5%/y [95% CI, −6.1% to −2.8%], P < .001). Clinical criteria were more sensitive in identifying sepsis than claims (69.7% [95% CI, 52.9% to 92.0%] vs 32.3% [95% CI, 24.4% to 43.0%], P < .001), with comparable positive predictive value (70.4% [95% CI, 64.0% to 76.8%] vs 75.2% [95% CI, 69.8% to 80.6%], P = .23).
Conclusions and Relevance
In clinical data from 409 hospitals, sepsis was present in 6% of adult hospitalizations, and in contrast to claims-based analyses, neither the incidence of sepsis nor the combined outcome of death or discharge to hospice changed significantly between 2009-2014. The findings also suggest that EHR-based clinical data provide more objective estimates than claims-based data for sepsis surveillance.
Purpose
The aim of this pilot study was to evaluate the potential of a new noninvasive optical measurement of muscle oxygenation (MOx) to identify shock severity in patients with suspected sepsis.
Methods
We enrolled 51 adult patients in the emergency department (ED) who presented with possible sepsis using traditional Systematic Inflammatory Response Syndrome criteria or who triggered a “Code Sepsis.” Noninvasive MOx measurements were made from the first dorsal interosseous muscles of the hand once potential sepsis/septic shock was identified, as soon as possible after admission to the ED. Shock severity was defined by concurrent systolic blood pressure, heart rate, and serum lactate levels. MOx was also measured in a control group of 17 healthy adults.
Results
Mean (± SD) MOx in the healthy control group was 91.0 ± 5.5% (n = 17). Patients with mild, moderate, and severe shock had mean MOx values of 79.4 ± 21.2%, 48.6 ± 28.6%, and 42.2 ± 4.7%, respectively. Mean MOx for the mild and moderate shock severity categories were statistically different from healthy controls and from each other based on two-sample t-tests (p < 0.05).
Conclusions
We demonstrate that noninvasive measurement of MOx was associated with clinical assessment of shock severity in suspected severe sepsis or septic shock. The ability of MOx to detect even mild septic shock has meaningful implications for emergency care, where decisions about triage and therapy must be made quickly and accurately. Future longitudinal studies may validate these findings and the value of MOx in monitoring patient status as treatment is administered.
Organ injury and impairment are commonly observed in patients with acute heart failure (AHF), and congestion is an essential pathophysiological mechanism of impaired organ function. Congestion is the predominant clinical profile in most patients with AHF; a smaller proportion presents with peripheral hypoperfusion or cardiogenic shock. Hypoperfusion further deteriorates organ function. The injury and dysfunction of target organs (i.e. heart, lungs, kidneys, liver, intestine, brain) in the setting of AHF are associated with increased risk for mortality. Improvement in organ function after decongestive therapies has been associated with a lower risk for post-discharge mortality. Thus, the prevention and correction of organ dysfunction represent a therapeutic target of interest in AHF and should be evaluated in clinical trials. Treatment strategies that specifically prevent, reduce or reverse organ dysfunction remain to be identified and evaluated to determine if such interventions impact mortality, morbidity and patient-centred outcomes. This paper reflects current understanding among experts of the presentation and management of organ impairment in AHF and suggests priorities for future research to advance the field.
Patients with malignancy comprise a unique group for whom transfusions play an important role. Because the need for transfusions may span a long period of time, these patients may be at risk for more adverse events due to transfusion than other patient groups.
A literature search on PubMed that included original studies and reviews was performed. The results were summarized and complemented by our clinical experience. Long-term complications of transfusions, such as transfusion-associated graft-vs-host disease, alloimmunization, transfusion-related immunomodulation, and iron overload, are discussed.
Transfusion-related acute lung injury, transfusion-associated circulatory overload, and hemolytic transfusion reaction are deadly complications from transfusion. These adverse events have nonspecific presentations and may be missed or confused with a patient's underlying condition. Thus, a high level of suspicion and close monitoring of the patient during and following the transfusion is imperative. Common reactions (eg, febrile nonhemolytic transfusion reaction, allergic reaction) are not life threatening, but they may cause discomfort and blood product wastage.
Every transfusion carries risks of immediate and delayed adverse events. Therefore, oncologists should prescribe transfusion for patients with cancer only when absolutely necessary.
Partial least-squares (PLS) and second-derivative preprocessing were used to obtain estimates of myoglobin oxygen fractional saturation from diffuse reflectance spectra of solutions containing myoglobin, hemoglobin, and a scatterer. A computer model and solutions in vitro were used to simulate several physiological situations. The maximum standard error (SE) was 0.082 for these trials; myoglobin fractional saturation varies between 0 and 1. These results show that a statistical approach can differentiate two highly overlapping absorbance peaks in the presence of diffuse scatter. A robust PLS model was created by using a calibration set with a range of scattering coefficients and concentrations of hemoglobin. Second derivatives of the spectra were less affected by changes in scattering coefficients than were the original spectra. A linear scaling of PLS estimates produced accurate myoglobin saturations from in vitro prediction set spectra that had scattering and absorption coefficients both within and beyond the range represented by the calibration set. Preliminary estimates of myoglobin fractional saturation from spectra acquired from the rat hind limb suggest that this calibration set is appropriate for use in vivo.
Quantitative values for myoglobin oxygen fractional saturation were extracted from visible absorption spectra of myoglobin and hemoglobin solutions by analysis with three algorithms: classical least-squares, partial least-squares, and stagewise multiple linear regression. In an effort to mimic in vivo conditions, oxygen tensions and concentrations of myoglobin and hemoglobin solutions in separate cuvettes were varied independently. Transmission measurements were made through both cuvettes so that spectra contained contributions from both myoglobin and hemoglobin. Oxygen tensions in the myoglobin solutions spanned the rapidly varying region of the myoglobin oxygen saturation curve with pO2 ranging from 0 to 4.79 Torr, corresponding to fractional saturation values between 0 and 0.903. A range of hemoglobin oxygenations from fully oxygenated to fully deoxygenated was used. Estimation of myoglobin fractional saturation by the classical least-squares algorithm had a standard error (SEest) of 0.094, while the partial least-squares method resulted in an SEest of 0.070. Partial least-squares estimations resulted in an SEest of 0.041 when a limited wavelength range was used. The stagewise multiple linear regression method had an SEest of 0.052. Results indicate that stagewise regression and partial least-squares yielded estimates of myoglobin fractional saturation that were more accurate than those obtained from classical least-squares.
A method is described for measuring optical properties and deriving chromophore concentrations from diffuse reflection measurements at the surface of a turbid medium. The method uses a diffusion approximation model for the diffuse reflectance, in combination with models for the absorption and scattering coefficients. An optical fibre-based set-up, capable of measuring nine spectra from 400 to 1050 nm simultaneously, is used to test the method experimentally. Results of the analyses of phantom and in vivo measurements are presented. These demonstrate that in the wavelength range from 600 to 900 nm, tissue scattering can be described as a simple power dependence of the wavelength and that the tissue absorption can be accurately described by the addition of water, oxy- and deoxyhaemoglobin absorption.
Background:
Aggressive fluid resuscitation in trauma promotes deleterious effects such as clot disruption, dilutional coagulopathy and hypothermia. Animal studies suggest that permissive hypotension maintains appropriate organ perfusion, reduces bleeding and improves mortality. This review assesses the efficacy and safety of permissive hypotension in adult trauma patients with hemorrhagic shock.
Methods:
We searched the MEDLINE and EMBASE databases from inception to May 2017 for randomized controlled trials comparing permissive hypotension vs. conventional resuscitation following traumatic injury. We included pre-operative and intraoperative resuscitation strategies. The primary outcome was 30-day or in-hospital mortality. Secondary outcomes included blood product utilization, estimated blood loss and in-hospital complications. Pooling was performed with a random-effects model.
Results:
We screened 722 abstracts, from which five randomized trials evaluating 1158 patients were included. Blood pressure targets in the intervention arms varied from systolic BP 50 - 70 mmHg or MAP ≥ 50 mmHg as compared to systolic BP 65 - 100 mmHg or MAP ≥ 65 in the control arms. Two studies evaluated only patients with penetrating injury while the remaining three additionally included blunt injuries. Four trials suggested a survival benefit for 30-day or in-hospital mortality with hypotensive resuscitation, although three studies were insufficiently powered to find statistical significance. Studies were of poor to moderate quality due to poor protocol reporting and lack of blinding. The pooled odds ratio was 0.70 (95% CI 0.53 to 0.92), suggesting a survival benefit for permissive hypotension. Those patients received fewer blood products and had lesser estimated blood loss.
Conclusion:
Permissive hypotension may offer a survival benefit over conventional resuscitation for patients with hemorrhagic injury. It may additionally reduce blood loss and blood product utilization. However, the majority of studies were underpowered, thus reflecting a need for high quality, adequately powered trials.
Level of evidence:
Systematic Review, Level II PROSPERO REGISTRATION: CRD42017070526.
Introduction:
We evaluated the potential utility of a new prototype noninvasive muscle oxygenation (MOx) measurement for the identification of shock severity in a population of patients admitted to the trauma resuscitation rooms of a Level I regional trauma center. The goal of this project was to correlate MOx with shock severity as defined by standard measures of shock: systolic blood pressure, heart rate, and lactate.
Methods:
Optical spectra were collected from subjects by placement of a custom-designed optical probe over the first dorsal interosseous muscles on the back of the hand. Spectra were acquired from trauma patients as soon as possible upon admission to the trauma resuscitation room. Patients with any injury were eligible for study. MOx was determined from the collected optical spectra with a multi-wavelength analysis that used both visible and near-infrared regions of light. Shock severity was determined in each patient by a scoring system based on combined degrees of hypotension, tachycardia, and lactate. MOx values of patients in each shock severity group (mild, moderate, and severe) were compared using two-sample t-tests.
Results:
In 17 healthy control patients, the mean MOx value was 91.0 ± 5.5%. A total of 69 trauma patients were studied. Patients classified as having mild shock had a mean MOx of 62.5 ± 26.2% (n = 33), those classified as in moderate shock had a mean MOx of 56.9 ± 26.9% (n = 25) and those classified as in severe shock had a MOx of 31.0 ± 17.1% (n = 11). Mean MOx for each of these groups was statistically different from the healthy control group (p < 0.05).Receiver operating characteristic (ROC) analyses show that MOx and shock index (heart rate/systolic blood pressure) identified shock similarly well (area under the curves (AUC) = 0.857 and 0.828, respectively). However, MOx identified mild shock better than shock index in the same group of patients (AUC = 0.782 and 0.671, respectively).
Conclusions:
The results obtained from this pilot study indicate that MOx correlates with shock severity in a population of trauma patients. Noninvasive and continuous MOx holds promise to aid in patient triage and to evaluate patient condition throughout the course of resuscitation.
Sepsis is a severe critical illness syndrome that arises from infectious insults. While the host immune system is generally beneficial, an overshooting and unregulated immune response can cause serious organ tissue injury. During sepsis, systemic hypotension, disturbed perfusion of the microcirculation, and direct tissue-toxicity caused by inflammatory immune reaction can occur and contribute to organ failure. The failure of two or more vital organ systems is termed multi-organ dysfunction syndrome (MODS) and resembles a very critical condition associated with high morbidity and mortality. Importantly, no specific treatment strategy exists to efficiently prevent the development of MODS during sepsis. In this review, we aim to identify the relevant molecular immunological pathways involved in the pathogenesis of MODS during sepsis. We believe that a detailed understanding of this mechanism is necessary for the development of new treatment approaches for septic patients. In particular, knowledge of the endogenous regulators keeping the balance between necessary immune system activation to combat infections and prevention of host tissue damage would greatly improve the chances for the development of effective interventions.
Near-infrared spectroscopy (NIRS) is non-invasive, easy to use, and offers real-time monitoring of the oxygen content of cerebral tissue. An effective and user-friendly method of cerebral monitoring stands to offer a significant advance in patient care during adult cardiac surgery, particularly for surgery in which the continuity of cerebral vessels may be compromised. While the current evidence does not definitively show improvement in neurological outcomes, it can be argued that the overall risk to benefit ratio falls on the side of NIRS. NIRS also gives information about the oxygenation of systemic tissues. It may be that in surgery that does not involve the aortic arch, the value of NIRS will be in increased individualisation of patient management and improved systemic perfusion, impacting general outcomes as much as neurological outcomes. This review will summarise the need for neuromonitoring and the principles of NIRS. It will examine the thresholds used to define desaturation, the evidence for clinical benefit from NIRS, and the criticisms and limitations of NIRS. It will also discuss the uses of NIRS beyond improving neurological outcomes alone.
Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.
In today's chemical industry there is a great need to both improve the effectiveness of existing assets and generate new prospects for business renewal. In addition, the fast pace of the current ‘information age’ makes it necessary to bring about both of these in a rapid and responsive manner in order to be competitive. On-line spectroscopic techniques, which provide rapid and representative information on a chemical process, are inherently capable of facilitating both asset productivity and business renewal. Chemometric ‘tools’, in principle, are particularly well suited for improving the effectiveness of on-line spectroscopic techniques through two main functions: (1) extracting the wealth of useful, yet convoluted information that is available from such techniques; and (2) facilitating the automation of on-line analytical techniques, at a time when manufacturing plant support resources are being ‘cut back’. Multivariate calibration tools can be used to improve the performance of existing methods, as well as to prepare more stable methods for new applications. More ‘soft’ modeling tools, such as multivariate curve resolution, are particularly well suited for providing timely information during the early stages of new process development, where very little is known about the process chemistry and dynamics. In practice, however, there is a wide range of issues, both technical and non-technical, that limit and even prevent the successful application of chemometric techniques for on-line spectroscopy. This paper will illustrate both the means by which chemometric tools can make a difference in the chemical industry, and the issues that are preventing its successful implementation, using examples from actual process development projects and on-line measurements. Copyright © 2000 John Wiley & Sons, Ltd.
In the severely injured who survive the early posttraumatic phase, multiple-organ failure (MOF) is the main cause of morbidity and mortality. An enhanced prediction of MOF might influence individual monitoring and therapy of severely injured patients.
We performed a retrospective analysis of a nationwide prospective database, the TraumaRegister DGU of the German Trauma Society. Patients with complete data sets (2002-2011) and a relevant trauma load (Injury Severity Score [ISS] ≥ 16), who were admitted to an intensive care unit, were included.
Of a total of 31,154 patients enclosed in this study, 10,201 (32.7%) developed an MOF according to the Sequential Organ Failure Assessment score. During the study period, mortality of all patients decreased from 18.1% in 2002 to 15.3% in 2011 (p < 0.001). Meanwhile, MOF occurred significantly more often (24.6% in 2002 vs. 31.5% in 2011, p < 0.001), but mortality of MOF patients decreased (42.6% vs. 33.3%, p < 0.001). MOF patients who died survived 2 days less (11 days in 2002 vs. 8.9 days in 2011, p < 0.001). Independent risk factors for the development of MOF following severe trauma were age, ISS, head Abbreviated Injury Scale (AIS) score of 3 or higher, thoracic AIS score of 3 or higher, male sex, Glasgow Coma Scale (GCS) score of 8 or less, mass transfusion, base excess of less than -3, systolic blood pressure less than 90 mm Hg at admission, and coagulopathy.
Over one decade, we observed an ongoing decrease of mortality after multiple trauma, accompanied by decreasing mortality in the subgroup with MOF. However, incidence of MOF in the severely injured increased significantly. Thus, MOF after multiple trauma remains a challenge in intensive care. The risk factors from multivariate analysis could be instrumental in anticipating the early development of MOF. Furthermore, a reliable prediction model might be supportive for patient enrolment in trauma studies, in which MOF marks the primary end point.
Epidemiologic study, level III.
Initially known as multiple system organ failure, the term multiple organ dysfunction syndrome (MODS) was first described in the 1960s in adults with bleeding, respiratory failure, and sepsis. It is defined as "the development of potentially reversible physiologic derangement involving two or more organ systems not involved in the disorder that resulted in ICU admission, and arising in the wake of a potentially life threatening physiologic insult."(3) There are many risk factors predisposing to MODS; however, the most common risk factors are shock due to any cause, sepsis, and tissue hypoperfusion. A dysregulated immune response, or immuneparalysis, in which the homeostasis between pro-inflammatory and anti-inflammatory reaction is lost is thought to be key in the development of MODS. The clinical course and evolution of MODS is dependent on a combination of acquired and genetic factors. There are several nonspecific therapies for the prevention and resolution of MODS, mostly care is supportive. Mortality from MODS in septic pediatric patients varies between 11% and 54%.
Myoglobin is an important intracellular protein found in cardiac and skeletal muscle. It is involved in the intracellular transport of oxygen from the cell membrane to the mitochondria where oxidative phosphorylation takes place. The optical absorbance characteristics of myoglobin are similar to those of hemoglobin in the nearinfrared spectral region. Distinguishing spectral information of myoglobin from hemoglobin should allow for determination of intracellular oxygen availability in muscle. Partial least-squares analysis is used in this report to determine the oxygen saturation of myoglobin, in the presence of hemoglobin, in vitro. Studies were performed with the use of both transmission and reflectance spectroscopic techniques. Transmission spectra of myoglobin solutions were determined with varying degrees of oxygen saturation achieved by deoxygenating the solution using E. coli. Calibration spectral data sets were developed with the use of varying concentrations of hemoglobin interference, and with varying degrees of myoglobin oxygen saturation. Reflectance spectra were obtained from myoglobin and hemoglobin solutions containing a scattering agent to mimic muscle tissue conditions. Predicted myoglobin saturation values were within 2% of the known saturation values from the use of this analysis. Partial least-squares analysis allows for accurate prediction of myoglobin oxygen saturation in the presence of hemoglobin from either transmission of reflectance near-infrared spectra.
A fiber-optic-based spectrophotometer was developed to acquire optical reflectance spectra from a living dog heart. A bullseye concentric optical probe with a 3 mm source-to-detector fiber separation was designed to obtain a 1.5 mm average tissue depth of light penetration. Spectra were analyzed in the near-infrared region from 660 to 840 nm. Myoglobin oxygen saturation was determined by partial least-squares analysis using a calibration spectral data set developed in vitro. Comparison of in vivo and in vitro spectra by Mahalanobis distance and residual ratio tests demonstrated good similarity, justifying use of partial least-squares analysis. Coronary perfusion with an oxygenated blood substitute, Fluosol , was used to demonstrate that hemoglobin had little effect on the analysis. An increase in myoglobin saturation of 5% was noted when the animals were changed from inspired room air to 100% oxygen. Occlusion of the coronary artery resulted in prompt decrease in myoglobin saturation, and release of the occlusion was followed by rapid increase in saturation to a value above baseline. These experiments demonstrate that it is feasible to use partial least-squares analysis of near-infrared reflectance spectra to determine myoglobin saturation in the blood-perfused, beating heart.
A technique for pattern recognition analysis of near-infrared reflectance spectra is described. Classification of samples is achieved by using the Mahalanobis distances of spectra in a principal component subspace. Probability levels for class membership are determined from the Chi-squared distribution.
Background:
Near-infrared spectroscopy is used during cardiac surgery to monitor the adequacy of cerebral perfusion. In this systematic review, we evaluated available data for adult patients to determine (1) whether decrements in cerebral oximetry during cardiac surgery are associated with stroke, postoperative cognitive dysfunction (POCD), or delirium; and (2) whether interventions aimed at correcting cerebral oximetry decrements improve neurologic outcomes.
Methods:
We searched PubMed, Cochrane, and Embase databases from inception until January 31, 2012, without restriction on languages. Each article was examined for additional references. A publication was excluded if it did not include original data (e.g., review, commentary) or if it was not published as a full-length article in a peer-reviewed journal (e.g., abstract only). The identified abstracts were screened first, and full texts of eligible articles were reviewed independently by 2 investigators. For eligible publications, we recorded the number of subjects, type of surgery, and criteria for diagnosis of neurologic end points.
Results:
We identified 13 case reports, 27 observational studies, and 2 prospectively randomized intervention trials that met our inclusion criteria. Case reports and 2 observational studies contained anecdotal evidence suggesting that regional cerebral O(2) saturation (rSco(2)) monitoring could be used to identify cardiopulmonary bypass cannula malposition. Six of 9 observational studies reported an association between acute rSco(2) desaturation and POCD based on the Mini-Mental State Examination (n = 3 studies) or more detailed cognitive testing (n = 6 studies). Two retrospective studies reported a relationship between rSco(2) desaturation and stroke or type I and II neurologic injury after surgery. The observational studies had many limitations, including small sample size, assessments only during the immediate postoperative period, and failure to perform risk adjustments. Two randomized studies evaluated the efficacy of interventions for treating rSco(2) desaturation during surgery, but adherence to the protocol was poor in one. In the other study, interventions for rSco(2) desaturation were associated with less major organ injury and shorter intensive care unit hospitalization compared with nonintervention.
Conclusions:
Reductions in rSco(2) during cardiac surgery may identify cardiopulmonary bypass cannula malposition, particularly during aortic surgery. Only low-level evidence links low rSco(2) during cardiac surgery to postoperative neurologic complications, and data are insufficient to conclude that interventions to improve rSco(2) desaturation prevent stroke or POCD.
Cerebral oximetry is a noninvasive technology using near-infrared spectroscopy (NIRS) to estimate regional cerebral oxygen saturation. Although NIRS cerebral oximetry is being increasingly used in many clinical settings, interdevice technologic differences suggest potential variation in the ability to accurately acquire brain oxygenation signals. The primary objective of this study was to determine if NIRS-derived regional cerebral oxygen saturation measurements accurately account for oxygen saturation contamination from extracranial tissue.
Twelve healthy volunteers had each of three NIRS devices (FORE-SIGHT [CAS Medical Systems Inc; Brandford, CT], INVOS 5100C-PB [Covidien; Boulder, CO], and EQUANOX Classic 7600 [Nonin Medical Inc; Plymouth, MN]) randomly applied to the forehead. After this, a circumferential pneumatic head cuff was positioned such that when inflated, hypoxia-ischemia would be produced in the extracranial scalp tissue beneath the NIRS cerebral oximeters. Comparisons among the three devices were made of the NIRS measurements before and following hypoxia-ischemia produced in the scalp tissue with inflation of the head cuff.
The induction of extracranial hypoxia-ischemia resulted in a significant reduction in regional cerebral oxygen saturation measurements in all three NIRS devices studied. At 5 min postinflation of the pneumatic head cuff, the INVOS demonstrated a 16.6 ± 9.6% (mean ± SD) decrease from its baseline (P = 0.0001), the FORE-SIGHT an 11.8 ± 5.3% decrease from its baseline (P < 0.0001), and the EQUANOX a 6.8 ± 6.0% reduction from baseline (P = 0.0025).
Extracranial contamination appears to significantly affect NIRS measurements of cerebral oxygen saturation. Although the clinical implications of these apparent inaccuracies require further study, they suggest that the oxygen saturation measurements provided by cerebral oximetry do not solely reflect that of the brain alone.
Partial least-squares (PLS) methods for spectral analyses are related to other multivariate calibration methods such as classical least-squares (CLS), inverse least-squares (ILS), and principal component regression (PCR) methods which have been used often in quantitative spectral analyses. The PLS method which analyzes one chemical component at a time is presented, and the basis of each step in the algorithm is explained. PLS calibration is shown to be composed of a series of simplified CLS and ILS steps. This detailed understanding of the PLS algorithm has helped to identify how chemically interpretable qualitative spectral information can be obtained from the intermediate steps of the PLS algorithm. These methods for extracting qualitative information are demonstrated by use of simulated spectral data. The qualitative information directly available from the PLS analysis is superior to that obtained from PCR but is not complete as that which can be generated during CLS analyses. Methods are presented for selecting optimal numbers of loading vectors for both the PLS and PCR models in order to optimize the model while simultaneously reducing the potential for overfitting the calibration data. Outlier detection and methods to evaluate the statistical significance of results obtained from the different calibration methods applied to the same spectral data are also discussed.
There is increasing interest in the application of near infrared spectroscopy (NIRS) as a noninvasive monitor of cerebral oxygenation. This review will briefly describe the principles of NIRS and examine current evidence for its clinical application as a monitor of the adequacy of cerebral oxygenation in adults.
There has been a recent surge of interest in the clinical application of NIRS following studies that have quantified the benefits of NIRS-guided management of cerebral oxygenation during cardiopulmonary bypass. However, there are limited data to support its widespread application in other clinical scenarios. New NIRS systems are being introduced to the market and technological advancements have improved their accuracy and extended the range of variables measured.
NIRS offers noninvasive monitoring of cerebral oxygenation over multiple regions of interest in a wide range of clinical scenarios. It has many potential advantages over other neuromonitoring techniques, but further technological advances are necessary before it can be introduced more widely into clinical practice.
A method to simultaneously measure oxygenation in vascular, intracellular, and mitochondrial spaces from optical spectra acquired from muscle has been developed. In order to validate the method, optical spectra in the visible and near-infrared regions (600-850 nm) were acquired from solutions of myoglobin, hemoglobin, and cytochrome oxidase that included Intralipid as a light scatterer. Spectra were also acquired from the rabbit forelimb. Three partial least squares (PLS) analyses were performed on second-derivative spectra, each separately calibrated to myoglobin oxygen saturation, hemoglobin oxygen saturation, or cytochrome aa3 oxidation. The three variables were measured from in vitro and in vivo spectra that contained all three chromophores. In the in vitro studies, measured values of myoglobin saturation, hemoglobin saturation, and cytochrome aa3 oxidation had standard errors of 5.9%, 7.4%, and 12.2%, respectively, with little cross-talk between the in vitro measurements. In the progression from normal oxygenation to ischemia in the rabbit forelimb, hemoglobin desaturated first, followed by myoglobin, while cytochrome aa3 reduction occurred last. The ability to simultaneously measure oxygenations in the vascular, intracellular, and mitochondrial compartments will be valuable in physiological studies of muscle metabolism and in clinical studies when oxygen supply or utilization are compromised.
Neurologic dysfunction is a problem in patients with congenital heart disease. Near infrared spectroscopy (NIRS) may provide a real-time window into cerebral oxygenation. Enthusiasm for NIRS has increased in hopes of reducing neurologic dysfunction. However, potential gains need to be evaluated relative to cost and potential detriment of intervention before routine implementation. Responding to data in ways that seem intuitively beneficial can be risky when the long-term impact is unknown. Many centers, and even entire countries, have adopted NIRS as standard of care. Available data suggest that multimodality monitoring, including NIRS, may be a useful adjunct. However, the current literature on the use of NIRS alone does not demonstrate improvement in neurologic outcome. Data correlating NIRS findings with indirect measures of neurologic outcome or mortality are limited. Although NIRS has promise for measuring regional tissue oxygen saturation, the lack of data demonstrating improved outcomes limits the support for wide-spread implementation.
Myoglobin (Mb) saturation in individual subepicardial myocytes was determined by cryospectroscopy in dogs, cats, ferrets, rabbits, and rats. Mb saturation within 800 microns of the epicardium is not affected by quick freezing or absorption of light by cytochromes. The PO2 in equilibrium with Mb (PMbO2) was calculated from the Mb oxydissociation curve. The minimum PMbO2 found among the 1,000 cells examined was 2.5 Torr, at least five times the critical PO2 for cytochrome turnover in myocardium. The maximum PMbO2 found was about one-half that in subepicardial venules, suggesting a large change in PO2 between capillaries and the cytosol. PMbO2 was the same in right and left ventricles and was unchanged by moderate hemodynamic stress. Median PMbO2 was remarkably uniform among species (range, 4.3-7.0 Torr in 20 animals), even though left ventricular work per minute varied approximately 200-fold, heart rate about fivefold, and arterial O2 content about twofold. Relatively uniform Mb saturation below venous PO2 should accelerate release of O2 from capillaries, promote Mb-facilitated O2 diffusion, and minimize diffusive O2 shunting.
At a certain PO2 the rate of O2 consumption (VO2) becomes limited by O2 availability rather than energy demand. This PO2 may be defined as the critical PO2 (PcritO2) for the corresponding rate of cytochrome turnover. PcritO2 sets the minimum PO2 which convective and diffusive transport must defend. To date there have been no estimates of PcritO2 for VO2 in vivo, though the influence of O2 on redox ratios has been studied extensively in heart, liver and brain. Some contend that cytochrome a,a3 is highly reduced in tissue over the entire physiologic range of O2 tensions.1,2 Such reduction implies that tissue respiration should be strongly O2 dependent and that there should be no PcritO2 for VO2 in vivo. Chance and associates studied O2 binding to cytochrome a, a3 in brain in the presence and absence of CO.3 They interpret their data to mean that cytochrome a, a3 is almost fully oxidized in vivo and in vitro. Lubbers and associates found cytochrome a, a3 more than 95% oxidized in rat heart (personal communication). Highly oxidized a, a3 suggests that VO2 depends solely on redox and phosphorylation potentials above a PO2 negligible for O2 transport.
Myoglobin (Mb) saturation was measured spectroscopically in 1,950 randomly selected cells from dog gracilis muscles frozen in situ during the transition from rest to steady twitch contraction at approximately 70% maximum rate of O2 consumption (VO2max). Measurements were made at the center of muscle-cell profiles in cross section, with spatial resolution approximately 5 X 5 X 3 micron. PO2 was calculated from saturation by use of the oxymyoglobin dissociation curve. Flow increased more rapidly than VO2 (half-times 5 and 14 s, respectively). Mb saturation changed little through 15 s. Saturation was lowest at 30 s and rose somewhat between 30 s and steady state. The lowest intracellular PO2 at any time or location was 1.5 Torr, and only 5% of loci were below 2 Torr. Since 1.5 Torr is about 10 times the minimum PO2 required for the observed VO2 (Connett et al. An upper bound on the minimum PO2 for O2 consumption in red muscle in vivo. Adv. Exp. Med. Biol. In press.), neither anoxia nor hypoxia was present. The observed fall in saturation and intracellular PO2 during exercise permits Mb to 1) promote transcapillary O2 flux, 2) facilitate intracellular O2 diffusion, 3) minimize convective and diffusive shunting, and 4) buffer intracellular PO2 above the tension that limits cytochrome turnover.
Abstract A quantitative method of determining the content of myoglobin and hemoglobin in human muscle is described.
A piece of muscle, 1–4 g, is ground with dry ice, homogenized and extracted with 0.02 M phosphate buffer, pH 7.4. After being centrifuged at 15,000 × g, the solution is concentrated by dialysis against 25% polyethylene glycol solution. The hemoproteins are separated by gel filtration on Sephadex G 75, identified by the absorption spectra of their carbon monoxide compounds and quantitatively determined by the pyridine hemochrome method.
The content of hemoprotein is calculated as per cent of dry weight, the latter being determined on the original homogenate.
In an autopsy material, mainly consisting of patients in upper age-groups with chronic disease and modest physical activity, average values of 0.9 g myoglobin per 100 g dry muscle were found in hearts (left ventricle), whereas corresponding values for diaphragm, abdominal muscle and muscles of the thigh were 1.1, 1.6 and 2.2 g per 100 g dry muscle. It is assumed that values in healthy adults may well be somewhat higher. From these values it is calculated that the total amount of myoglobin in an adult male is in the range of 120–150 g, corresponding to an iron pool of 0.37-0.47 g or approximately 7/5 of the amount of hemoglobin iron.
Comparisons with determinations arrived at by other methods are made, and some aspects of the physiology of myoglobin and other hematin compounds are discussed.
The insoluble or “residual” hematin has been determined. It could be shown that the major part of this hematin can be accounted for by the mitochondrial hemoproteins, the remaining part in all probability deriving from hemoglobin.
The assumption that cellular oxygen pressure (PO2) is close to zero in maximally exercising muscle is essential for the hypothesis that O2 transport between blood and mitochondria has a finite conductance that determines maximum O2 consumption. The unique combination of isolated human quadriceps exercise, direct measures of arterial, femoral venous PO2, and 1H nuclear magnetic resonance spectroscopy to detect myoglobin desaturation enabled this assumption to be tested in six trained men while breathing room air (normoxic, N) and 12% O2 (hypoxic, H). Within 20 s of exercise onset partial myoglobin desaturation was evident even at 50% of maximum O2 consumption, was significantly greater in H than N, and was then constant at an average of 51 +/- 3% (N) and 60 +/- 3% (H) throughout the incremental exercise protocol to maximum work rate. Assuming a myoglobin PO2 where 50% of myoglobin binding sites are bound with O2 of 3.2 mmHg, myoglobin-associated PO2 averaged 3.1 +/- .3 (N) and 2.1 +/- .2 mmHg (H). At maximal exercise, measurements of arterial PO2 (115 +/- 4 [N] and 46 +/- 1 mmHg [H]) and femoral venous PO2 (22 +/- 1.6 [N] and 17 +/- 1.3 mmHg [H]) resulted in calculated mean capillary PO2 values of 38 +/- 2 (N) and 30 +/- 2 mmHg(H). Thus, for the first time, large differences in PO2 between blood and intracellular tissue have been demonstrated in intact normal human muscle and are found over a wide range of exercise intensities. These data are consistent with an O2 diffusion limitation across the 1-5-microns path-length from red cell to the sarcolemma that plays a role in determining maximal muscle O2 uptake in normal humans.
The use of a pulse oximeter to monitor arterial oxygen saturation (SaO2) is considered accurate and reliable in the range of 90% to 100%. However, differing reports exist about the accuracy with desaturation. Thus, the suitability of pulse oximetry in desaturated patients was evaluated using a Nellcor N-100 oximeter. In 56 children with cyanotic congenital heart disease, the pulse oximeter reading was compared with the direct measurement of SaO2 by a CO-oximeter OSM 3. The influence of high hematocrit values on the accuracy at low saturation was also investigated. All oxygen saturation measurements (two per child) were carried out after induction of anesthesia (ketamine, fentanyl, pancuronium) during a "steady state" before the surgical procedure. The results indicate that at low levels of saturation (SaO2 below 80%), pulse oximetry is not as accurate as at higher saturations, and overestimates the true value. Bias and precision between saturations measured by the pulse oximeter and the CO-oximeter were 5.8 and 4.8 in the group with a saturation below 80%, and 0.5 and 2.5 in the group with a saturation over 90%, respectively. Because the margin of safety for a patient is small when arterial saturation levels are under 80%, it is advisable under this condition to check the SaO2 measurements by a CO-oximeter. High hematocrit levels did not seem to be responsible for impaired accuracy of pulse oximetry at saturation values below 80%.
Multiwavelength optical spectroscopy was used to determine the oxygen-binding characteristics for equine myoglobin. Oxygen-binding relationships as a function of oxygen tension were determined for temperatures of 10, 25, 35, 37, and 40 degrees C, at pH 7.0. In addition, dissociation curves were determined at 37 degrees C for pH 6.5, 7.0, and 7.5. Equilibration was achieved with a myoglobin solution, at the desired temperature and pH, and 16 oxygen-nitrogen gas mixtures of known oxygen fraction. Correction for the inevitable presence of metmyoglobin was made by using a three-component least squares analysis and by correcting the end point oxymyoglobin spectra for the presence of metmyoglobin. The PO2 at which myoglobin is half-saturated with O2 (P50) was determined to be 2.39 Torr at pH 7.0 and 37 degrees C. The myoglobin dissociation curve was well fit by the Hill equation [saturation = PO2/(PO2 + P50)].
To evaluate the performance of two pulse oximeters in the measurement of arterial hemoglobin saturation in hypoxemic children.
Prospective, repeated-measures observational study.
A 16-bed pediatric intensive care unit in a children's tertiary hospital.
Sixty-six patients with arterial saturation of <90%.
Three arterial blood samples were taken from each subject during a 48-hr period. Pulse oximeter measurements of arterial saturation were compared with arterial saturation determined by cooximetry.
Arterial saturation was measured using one or both pulse oximeters (SpO2) and compared with the arterial hemoglobin saturation determined by cooximetry (SaO2). Sixty-two subjects were studied, using the Ohmeda pulse oximeter giving 185 data points (78 with saturations <75% [defined by the average of pulse oximeter and cooximeter]); 53 subjects were studied, using the Hewlett-Packard pulse oximeter yielding 155 data points (60 with saturations <75%). SpO2 ranged from 24% to 94%. Bias and precision of the Ohmeda pulse oximeter were -2.8% and 4.8% >75% and -0.8% and 8.0% <75%. Bias and precision of the Hewlett-Packard pulse oximeter were -0.5% and 5.1% >75% and 0.4% and 4.6% <75%. Intrapatient regression coefficient (r) for the differences between pulse oximeter and cooximeter was 0.58 for the Ohmeda and 0.59 for the Hewlett-Packard. Regression coefficients for predicting change in cooximeter value given a change in the Ohmeda pulse oximeter were 0.59 and 0.71 <75% and >75%, respectively. Similar coefficients for the Hewlett-Packard pulse oximeter were 0.50 and 0.70, respectively.
The performance of the Ohmeda pulse oximeter deteriorated below an SpO2 of 75%. The Hewlett-Packard pulse oximeter performed consistently above and below an SpO2 of 75%. The ability of both pulse oximeters to reliably predict change in SaO2 based on change in pulse oximetry was limited. We recommend measurement of PaO2 or SaO2 for important clinical decisions.
Skeletal muscles consist of slow-twitch and fast-twitch muscle fibers, which have distinct physiological and biochemical properties. The muscle fiber composition determines the contractile velocity and fatigability of a particular skeletal muscle. We analyzed the systemic distribution of slow muscle fibers in all rodent skeletal muscles by myosin ATPase staining and found that only seven hindlimb skeletal muscles were extremely rich in slow muscle fibers. These included the mouse piriformis (56.5%), gluteus minimus (35.7%), vastus intermedius (24.7%), quadratus femoris (69.9%), adductor brevis (44.3%), gracilis (24.6%), and soleus muscles (35.1%). In mice, the relative proportion of slow muscle fibers did not exceed 15% in skeletal muscles in other regions. The distribution of slow muscle fibers was well conserved in rats and rabbits. The soleus muscle is an important antigravity muscle in both rodents and humans; therefore, these skeletal muscles rich in slow muscle fibers might play an important role in sustaining neutral alignment of the lower extremity.
Intracellular oxygen (O2) availability and the impact of ambient hypoxia have far reaching ramifications in terms of cell signalling and homeostasis; however, in vivo cellular oxygenation has been an elusive variable to assess. Within skeletal muscle the extent to which myoglobin desaturates (deoxy-Mb) and the extent of this desaturation in relation to O2 availability provide an endogenous probe for intracellular O2 partial pressure (P(iO2)). By combining proton nuclear magnetic resonance spectroscopy (1H NMRS) at a high field strength (4 T), assessing a large muscle volume in a highly efficient coil, and extended signal averaging (30 min) we assessed the level of skeletal muscle deoxy-Mb in 10 healthy men (30 +/- 4 years) at rest in both normoxia and hypoxia (10% O2). In normoxia there was an average deoxy-Mb signal of 9 +/- 1%, which, when converted to P(iO2) using an O2/Mb half-saturation (P50) of 3.2 mmHg, revealed an P(iO2) of 34 +/- 6 mmHg. In ambient hypoxia the deoxy-Mb signal rose to 13 +/- 3% (P(iO2) = 23 +/- 6 mmHg). However, intersubject variation in the defence of arterial oxygenation (S(aO2)) in hypoxia (S(aO2) range: 86-67%) revealed a significant relationship between the changes in S(aO2) and P(iO2)(r2 = 0.5). These data are the first to document resting intracellular oxygenation in human skeletal muscle, highlighting the relatively high P(iO2) values that contrast markedly with those previously recorded during exercise (approximately 2-5 mmHg). Additionally, the impact of ambient hypoxia on P(iO2) and the relationship between changes in S(aO2) and P(iO2) stress the importance of the O2 cascade from air to cell that ultimately effects O2 availability and O2 sensing at the cellular level.
The aim of this study was to examine the effects of assuming constant reduced scattering coefficient (mu'(s)) on the muscle oxygenation response to incremental exercise and its recovery kinetics. Fifteen subjects (age: 24 +/- 5 yr) underwent incremental cycling exercise. Frequency domain near-infrared spectroscopy (NIRS) was used to estimate deoxyhemoglobin concentration {[deoxy(Hb+Mb)]} (where Mb is myoglobin), oxyhemoglobin concentration {[oxy(Hb+Mb)]}, total Hb concentration (Total[Hb+Mb]), and tissue O(2) saturation (Sti(O(2))), incorporating both continuous measurements of mu'(s) and assuming constant mu'(s). When measuring mu'(s), we observed significant changes in NIRS variables at peak work rate Delta[deoxy(Hb+Mb)] (15.0 +/- 7.8 microM), Delta[oxy(Hb+Mb)] (-4.8 +/- 5.8 microM), DeltaTotal[Hb+Mb] (10.9 +/- 8.4 microM), and DeltaSti(O(2))(-11.8 +/- 4.1%). Assuming constant mu'(s) resulted in greater (P < 0.01 vs. measured mu'(s)) changes in the NIRS variables at peak work rate, where Delta[deoxy(Hb+Mb)] = 24.5 +/- 15.6 microM, Delta[oxy(Hb+Mb)] = -9.7 +/- 8.2 microM, DeltaTotal[Hb+Mb] = 14.8 +/- 8.7 microM, and DeltaSti(O(2))= -18.7 +/- 8.4%. Regarding the recovery kinetics, the large 95% confidence intervals (CI) for the difference between those determine measuring mu'(s) and assuming constant mu'(s) suggested poor agreement between methods. For the mean response time (MRT), which describes the overall kinetics, the 95% confidence intervals were MRT - [deoxy(Hb+Mb)] = 26.7 s; MRT - [oxy(Hb+Mb)] = 11.8 s, and MRT - Sti(O(2))= 11.8 s. In conclusion, mu'(s) changed from light to peak exercise. Furthermore, assuming a constant mu'(s) led to an overestimation of the changes in NIRS variables during exercise and distortion of the recovery kinetics.
Design and Performance Validation of Phantoms Used in Conjunction with Optical Measurement of Tissue VI
- K M Asplund
- K A Schenkman
- W A Ciesielski
- L S L Arakaki
National Hospital Ambulatory Medical Care Survey: 2015 Emergency Department Summary Tables
- P Rui
- K Kang
“Adipose Tissue Thickness Affects In Vivo Quantitative Near-IR Spectroscopy in Human Skeletal Muscle”
- M C Van Beekvelt
- M S Borghuis
- B G Van Engelen
- R A Wevers
- W N Colier