TY - JOUR
AU - FRCSC, Joel S. Fish, MD, MSc,
AB - Abstract A lack of noninvasive tools to quantify edema has limited our understanding of burn wound edema pathophysiology in a clinical setting. Near-infrared spectroscopy (NIR) is a new noninvasive tool able to measure water concentration/edema in tissue. The purpose of this study was to determine whether NIR could detect water concentration changes or edema formation in acute partial-thickness burn injuries. Adult burn patients within 72 hours postinjury, thermal etiology, partial-thickness burn depth, and <20% TBSA were included. Burn wounds were stratified into partial-thickness superficial or deep wounds based on histology and wound healing time. NIR devices were used to quantify edema in a burn and respective control sites. The sample population consisted of superficial (n = 12) and deep (n = 5) partial-thickness burn injuries. The patients did not differ with respect to age (40 ± 15 years), TBSA (5 ± 4%), and mean time for edema assessment (2 days). Water content increased 15% in burned tissue compared with the respective control regions. There were no differences in water content at the control sites. At 48 hours, deep partial-thickness injuries showed a 23% increase in water content compared with 18% superficial partial-thickness burns. NIR could detect differences in water content or edema formation in partial-thickness burns and unburned healthy regions. NIR holds promise as a noninvasive, portable clinical tool to quantify water content or edema in burn wounds. Our research group has been investigating the utility of near-infrared spectroscopy (NIR) to measure burn depth since 2001.1,–3 This advanced technology has the capacity to assess the physiologic parameters in tissue, specifically oxygen saturation and blood volume, by simply illuminating the tissue with light and measuring the reflected signal. Specifically, as light travels from a fiber optic through tissue, a portion is absorbed by tissue chromophores and the attenuated light measured by a series of optical fibers. This light is relayed to a spectrometer, which disperses the light into wavelengths and, thus, a spectrum. There are specific wavelengths in the visible and NIR region where the chromophores (oxyhemoglobin, deoxyhemoglobin, and melanin) absorb light, and using this information the relative concentrations of the chromophore can be determined. This technology is based on the Beer-Lambert Law, and its principles have been well documented for more than a century.2 This light-based technology poses no risk to the patient or the operator, and therefore the modality can be used at the bedside. This feature is especially important for burn patients, because they can be medically unstable for repeated transports to an imaging suite. Major burn patients are immunosuppressed, at high risk of infection, and housed in regulated pressure isolation rooms to reduce the risk of infection.4 A wound assessment technology needs to be compatible with this environment and requires the ability to be brought to the patient to limit their exposure to nosocomial infections. This technology has peaked our interest and the interest of others, because it has shown promise in determining the end points of resuscitation, as a predictor of organ dysfunction, and cerebral oxygenation.5,–10 Interestingly, no one has described NIR's capacity to measure water concentration or edema in wounded tissue. In fact, water is the dominant signal in NIR spectroscopy and is often considered a nuisance to some chemists. This is particularly true when determining the chemical composition for compounds that have spectra in the water region. In these spectral regions, where water is predominant, the signal of other compounds in the spectrum is overshadowed by a strong water absorption peak. The determination of moisture in food analysis was one of the first applications of NIR. In some analysis, to eliminate the absorption spectra of water, the samples need to be completely free of water and are dried before being analyzed.11 This feature of NIR technology to accurately measure water lends well to the assessment of water content in tissue. The presence of edema is not only a skin phenomenon but also can occur in any organ. Pulmonary, cerebral, and intestinal edema can impact on patient mortality and are difficult to monitor noninvasively or require transportation to an imaging modality.12,–14 Chronic edema or lymphedema affects the morbidity or function of patients with conditions such as chronic wounds or postnodectomy surgery for tumor excision.15,16 There are few areas of medicine that are not affected by edema. The application of a noninvasive tool, such as NIR, to measure edema in tissue has applications that extend well beyond the realm of burn injury. Demling stated in 2005, one of the “major obstacles to improving our knowledge of the pathophysiology of burn edema has been the difficulty in quantifying edema.” The majority of our knowledge about burn edema is derived from animal models because of a lack of noninvasive and accurate techniques to quantify edema in a clinical setting.17 The capacity of a noninvasive technology to quantify water content accurately at the bedside would be a valuable tool and would be the first of its kind. Measuring edema is important, because edema has been shown to affect survival, limit the oxygenation to the burn wound, increase infection risk, and impact the progression of burn injury. Several groups, including our own, have used NIR to measure hydration in normal skin, but very little is known about its capacity to measure water accumulation or edema formation in burn injuries.18,–24 The purpose of this study was to evaluate NIR as a clinical tool to determine the water content or edema in burn wounds, specifically partial-thickness burn wounds. MATERIALS AND METHODS Study Overview This is a prospective, nonrandomized study in patients admitted to an adult regional burn centre. This study was approved by the human research ethics boards at both the institutions. Patient Population The patient population is comprises two groups: burn patients and nonburn healthy subjects. Adult burn patients presenting to the burn unit between November 2004 and October 2005 were eligible for the study. Subjects with acute burns less than 72 hours postinjury, thermal etiology, <20% TBSA, and partial-thickness burn depth were included. Large TBSA burn patients were not included, because it is difficult to find a healthy unburned region not affected by edema due to the systemic effects of the burn injury.25 Large TBSA burns also require a large volume resuscitation, which could directly impact the levels of water or edema in the wounds. Therefore, none of the subjects included in the study required fluid resuscitation. Subjects with chemical or electrical etiology burns were excluded. Chemical and electrical burns have a unique pathophysiology compared with that of a thermal injury and, for consistency, were excluded.26 Healthy subjects were recruited for the study using a flyer posted in the hospital. Exclusion criteria included subjects with preexisting medical conditions, such as diseases caused by a neurologic or vascular causal factor, endocrine disorders, infections, and acute or chronic wounds. Smokers and recreational drug and alcohol abusers were also excluded. Study Design Burn subjects were identified by the attending physician or surgeon and referred to the study coordinator. If the patient was deemed appropriate for the study, voluntary and written consent was obtained, and a time was coordinated with nursing staff for dressing removal. Patients were premedicated with narcotics 30 minutes before the dressing change as per the standing orders from the physician. During this time, the devices were specifically calibrated and covered with a clear plastic cover before entry into the regulated pressure isolation rooms. The patient was placed in a supine position to remove the dressings and any residual cream. It is routine practice in our burn centre to treat partial-thickness injuries with silver sulfadiazine (Flamazine™; Smith and Nephew, United Kingdom) cream, unless there is a contraindication for usage. An area within the burn wound was chosen for the study along with a respective healthy control site (called the local control). The local control region was considered to be one joint proximal or distal to the burned region or a contralateral skin surface. Local controls were felt to be necessary to account for the normal fluctuation of water content within individuals and between individuals. Nonburn healthy subjects were acclimatized in the study environment for 15 minutes before study measurement. The anatomic region of interest, the dorsal forearm, was outlined using an indelible marker, and data were collected with the subject in a supine position. Measurements, using two NIR devices (described below), were acquired from a burn and respective control site in burn patients and from the dorsal forearm in healthy subjects. Digital photographs were acquired at the time of data collection to document the clinical appearance of the sites of interest. Edema Measurement Devices Near-Infrared Point Spectroscopy. The first device, NIR point spectroscopy, is a handheld probe that gently rests on the subject's skin (Figure 1). A sterile polyurethane transparent sheath is placed over the probe before skin contact. This sheath allows the penetration of NIR light and does not interfere with light transmitted from the tissue. Three measurements were collected with the probe from the central portion of the burn wound and the healthy adjacent nonburned control site. It takes 16 seconds to acquire each NIR probe measurement. Figure 1. View largeDownload slide Near-infrared point spectroscopy device is a handheld probe that rests on the skin. Figure 1. View largeDownload slide Near-infrared point spectroscopy device is a handheld probe that rests on the skin. The point spectroscopy is designed as a small unit that contains a light source, a set of optical fibers to deliver light to the skin and collect reflected light from the tissue. It contains an imaging spectragraph to disperse the captured reflected light into its spectrum and a charge-coupled device detector to record the spectrum over the 500 to 1100 nm wavelength range (Sciencetech, Inc., London, Ontario, Canada). A 100-W quartz tungsten halogen white light source model 77501 (Oriel, Strattford, CT) was used in conjunction with a multifiber optic bundle (Fiberguide Industries, Stirling, NJ) that consisted of one fiber to deliver the light to the tissue and four detection optical fibers at the entrance slit of the imaging spectrograph. The detection fibers are displaced by regular intervals (1.5 mm, 3 mm, 4.5 mm, and 6 mm) from the light delivery fiber (Figure 2). In this configuration, light gathered by the sequence of detection fibers samples different volumes of tissue. The greater the separation or interval between the light delivery fiber and the collection fiber, the deeper the light penetrates into the tissue. Detector 0 is a surface wound detector, 1 and 2 are considered the dermal detectors, and detector 3 is a deep tissue collector. For the purposes of this study, only detector 1, 2, and 3 results are reported. The data collected from detector 0 are not included, because the reflected light captured by this detector measures the surface or near surface water content. Raw reflectance measurements were converted to optical density units through a ratio of the tissue reflectance against a 99% Spectralon® reflectance standard (LabSphere, Inc., North Sutton, NH) before data processing. Figure 2. View largeDownload slide Near-infrared point spectroscopy probe schematic. Light from a fiber optic illuminates the skin. Light takes a path through the tissue and is collected by a series of fiber optic detectors. The further the distance from the light source, the deeper the tissue information collected. Figure 2. View largeDownload slide Near-infrared point spectroscopy probe schematic. Light from a fiber optic illuminates the skin. Light takes a path through the tissue and is collected by a series of fiber optic detectors. The further the distance from the light source, the deeper the tissue information collected. Near-Infrared Imaging Spectroscopy. The second device, NIR imaging, is a camera suspended above the area of interest and does not touch the skin (Figure 3). The NIR imaging device can capture a larger surface area of the burn in comparison with the NIR point device. Digital NIR images were collected from a burn site and healthy control site. One sequence of NIR images can be acquired within 60 seconds. Figure 3. View largeDownload slide Near-infrared imaging device is a camera-based system that is suspended above the burn wound. Figure 3. View largeDownload slide Near-infrared imaging device is a camera-based system that is suspended above the burn wound. The NIR imaging device design is a camera, which takes a sequence of digital images of 532 × 256 pixels between 650 and 1050 nm at 10-nm increments using a back-thinned full frame transfer charge-coupled device camera (Hamamatsu, Newark, NJ). This camera is fitted with a Nikon Macro AF60 lens and a 7-nm bandpass (FWHH) Lyot-type liquid crystal tunable filter (Cambridge Research Instruments, Cambridge, MA). Two tungsten halogen lights were used to illuminate the area of interest, with the camera suspended approximately 60 cm above the area of interest. The device is calibrated initially using the image of the white side of a Kodak Gray Card (Rochester, NY). The NIR images are presented as grayscale images with a water content scale to the right of the image. Results are interpreted as dark or black regions representing minimal water content and light or white areas representing high water content. Burn Depth Determination and Study Endpoints The end points of the study were surgical intervention or time to complete wound healing. Histology is considered to be the reference standard for burn depth determination. Intraoperative biopsies were performed if the attending surgeon felt the patient required excision and grafting and was not influenced by enrollment in the study. Specimens were fixed in 10% formalin, bisected, and placed in paraffin, and then stained with hemoxylin and eosin and vimentin. Biopsies were then reviewed independently by two dermatopathologists blinded to the clinical diagnosis and NIR results. Not all patients require surgery for their burn wounds. In this patient population, biopsies could not be performed because of the risk of additional scarring and discomfort for the patient. These subjects were followed up daily until the burn wound was 100% reepithelialized. A partial-thickness burn was considered to be a superficial or viable injury if the wound healed in <3 weeks. If the wound took longer than 3 weeks to heal, it was considered to be a deep partial-thickness injury.18 Data Processing NIR technology data processing is based on a modified Beer-Lambert equation to relate the measured reflectance to the water content.9 Mathematical methods used to extract the water content from attenuated light rely on the scattering and absorption of light by tissue constituents. There are strong absorption peaks of water at 970 nm, 1450 nm, and 1920 nm, which represent OH bond stretching and HOH bands. For our laboratory and clinical studies, we use the 970-nm band as our water peak, because our device has a wavelength maximum of 1050 to 1100 nm. This is considered to be the second overtone for water and represents an OH stretch only. Spectra are initially converted from raw reflectance spectra to absorption by using the reflectance standard. There are several methodologies that can be used to extract water content from light reflectance. The method applied in this article is a least squares estimate approach. The absorption spectrum in the 900 to 1000 nm region is assumed to be a linear combination of components, namely, the absorption spectra water, a wavelength-dependent scattering component, and a baseline offset. The scattering and baseline components account for optical scattering properties of tissue. In other words, the spectrum measured with the device is the sum of a spectrum due to water present in the tissue, the scattering due to the tissue, and a baseline offset. Because we are assuming a linear combination of components, a least squares estimate of the components to the measured spectrum, expressed in optical density, provides a measure of the water concentration. The NIR point device provides the water content over different volumes at varying levels within the tissue, because light is collected from three depth-dependent detectors labeled 1 to 3. All computations were performed using MATLAB Version 6 (The Mathworks, Inc., South Natick, MA). Statistical Analysis Statistical analysis consisted of a χ2 analysis for nonparametric data. The means of three or more independent samples were compared using analysis of variance, and means of paired observations were compared using paired t-tests. These results are presented as mean ± 2 SE, with statistical significance achieved with a P value less than .05. All statistical computations were performed using SPSS version 14 (Chicago, IL). RESULTS There were 19 burn patients enrolled in the study and 11 healthy control subjects. Two burn patients were used to train the technician in the use of the NIR devices, leaving 17 available for analysis. There were no statistically significant differences between the demographics of the groups as given in Table 1. The anatomic regions of interest for the burn sites included the upper extremity (n = 10), lower extremity (n = 4), trunk (n = 2), and face (n = 1). The local control sites studied included the upper extremity (n = 8), lower extremity (n = 6), and trunk (n = 3). Measurements from the healthy subjects were acquired from the dorsal aspect of the subject's forearm, midway between the radial head and the distal radius. Table 1. Demographics of the burn and nonburn patient population View Large Table 1. Demographics of the burn and nonburn patient population View Large The 17 burn patients enrolled in the study were considered to have partial-thickness burn injuries by the attending physician at the time of enrollment into the study. The combination of histology and time to complete wound healing was used as the reference standard for burn depth determination and to perform the statistical analysis. Three patients did not consent to biopsies despite the fact that they required excision and grafting. These patients were placed in the deep partial-thickness category. Therefore, for the statistical analysis, 5 (n = 5) patients were considered to have deep partial-thickness injuries and 12 (n = 12) patients with superficial partial-thickness injuries. NIR point spectroscopy is designed with multiple detectors that collect NIR light reflecting from various depths in the tissue (Figure 2). The first statistical analysis compared the water content of superficial and deep partial-thickness burns at each detector position. The deep partial-thickness burns showed a statistically significant increase in water content compared with superficial partial-thickness burns at detectors 1 and 2 as depicted in Figure 4. However, no significant differences were noted at detector 3. When comparing the local control sites, there was no difference in the water content between the sites chosen for the controls of the superficial and deep partial-thickness injuries as shown in Figure 5. Water content was significantly elevated in the local control region compared with that of the healthy nonburned skin as given in Table 2. Figure 4. View largeDownload slide Mean water concentration for burn sites of superficial (n = 12) and deep partial-thickness burns (n = 5), demonstrating an increase in water concentration in deep partial-thickness burns compared with superficial partial-thickness burns at detector positions 1 (*P = .004) and 2 (**P = .010) but not at 3 (P = .150). Figure 4. View largeDownload slide Mean water concentration for burn sites of superficial (n = 12) and deep partial-thickness burns (n = 5), demonstrating an increase in water concentration in deep partial-thickness burns compared with superficial partial-thickness burns at detector positions 1 (*P = .004) and 2 (**P = .010) but not at 3 (P = .150). Figure 5. View largeDownload slide Mean water concentration for local control sites of superficial (n = 12) and deep partial-thickness burns (n = 5), demonstrating no differences in water concentration at detector positions 1 (P = .596), 2 (P = .516), and 3 (P = .375). Figure 5. View largeDownload slide Mean water concentration for local control sites of superficial (n = 12) and deep partial-thickness burns (n = 5), demonstrating no differences in water concentration at detector positions 1 (P = .596), 2 (P = .516), and 3 (P = .375). Table 2. Mean water content for healthy subjects and from the local control in patients with partial-thickness burns View Large Table 2. Mean water content for healthy subjects and from the local control in patients with partial-thickness burns View Large In the second statistical analysis, the burn depth categories were kept separate to compare water content differences for the local control site and burn wound. In superficial partial-thickness burns, the burn wound showed an increase in water content compared with the control site at all detectors as shown in Figure 6. For detector position 1, this is a 15% increase in water concentration in the burn wound compared with the control. Detector 2 and 3 showed an increase by 21 and 18%, respectively. In deep partial-thickness burns, the water content was elevated, compared with the control site, only at detectors 1 and 2 as shown in Figure 7. This represents an increase in water content of 19% at detector 1 and 23% at detector 2 within the burn site, when compared with the local control. Figure 6. View largeDownload slide Mean water concentration comparing burn and local control sites of superficial partial-thickness burns, demonstrating an increase in water concentration within the burn site at detector positions 1 (*P = .001), 2 (**P = .001), and 3 (†P = .005). Figure 6. View largeDownload slide Mean water concentration comparing burn and local control sites of superficial partial-thickness burns, demonstrating an increase in water concentration within the burn site at detector positions 1 (*P = .001), 2 (**P = .001), and 3 (†P = .005). Figure 7. View largeDownload slide Mean water concentration comparing burn and local control sites of deep partial-thickness burns, demonstrating an increase in water concentration within the burn site at detector positions 1 (*P = .023) and 2 (**P = .032) but not at 3 (P = .129). Figure 7. View largeDownload slide Mean water concentration comparing burn and local control sites of deep partial-thickness burns, demonstrating an increase in water concentration within the burn site at detector positions 1 (*P = .023) and 2 (**P = .032) but not at 3 (P = .129). The NIR imaging device could also measure water content within the burn injuries. A superficial partial-thickness burn and its respective control site are shown in Figure 8. These images can be interpreted according to the scale in gray that is included next to the images. The more white within the area of interest, the higher the water content, whereas a darker image represents lower water content. At postburn day 2, there is an obvious increase in water content in the forearm burn (area is lighter gray) compared with the healthy region surrounding the burn injury. In comparison, the control site (proximal thigh) did not contain a high content of water within this region. When comparing the NIR images of the healthy region adjacent to the burn (Figure 8B) and the control site (Figure 8C), it is clear that the burn has a higher water content compared with the distant site. Figure 9 represents a deep partial-thickness burn and its respective control site. When comparing the NIR images of the burn vs the control site, it is clear that the burn (Figure 9B) has an increased water concentration compared with the control site (Figure 9C). Interestingly, the control site for the deep partial-thickness burn showed an increased level of water concentration compared with the control site paired with the superficial partial-thickness burn site. Figure 8. View largeDownload slide Superficial partial-thickness burn. A, Digital photograph of burn region; B, NIR water image of burn region showing an increase in water in the burn site; C, Local control site showing no increase in water concentration. The superficial vasculature is also visualized in this image, as shown by the red arrow. Figure 8. View largeDownload slide Superficial partial-thickness burn. A, Digital photograph of burn region; B, NIR water image of burn region showing an increase in water in the burn site; C, Local control site showing no increase in water concentration. The superficial vasculature is also visualized in this image, as shown by the red arrow. Figure 9. View largeDownload slide Deep partial-thickness burn injury. A, Digital photograph of the burn wound; B, Burn wound showing water accumulation in the burn region; C, Local control region showing a small increase in water concentration. The superficial vasculature is also visible in both the burn and control regions. Figure 9. View largeDownload slide Deep partial-thickness burn injury. A, Digital photograph of the burn wound; B, Burn wound showing water accumulation in the burn region; C, Local control region showing a small increase in water concentration. The superficial vasculature is also visible in both the burn and control regions. DISCUSSION The application of NIR spectroscopy extends beyond the realm of medicine. Agriculture and food chemists have been using commercially available NIR systems to measure organic and inorganic compounds for many years.11 The advantage of NIR spectroscopy in this industry is that it is a multianalytical technique and can perform several determinations at once.27 However, to obtain an accurate assessment of samples, using soil as an example, the specimens need to be dried to eliminate the effects of water on the shape of the soil spectra.28 NIR spectroscopy is also used to measure the moisture content of dried food products such as cocoa and milk.29,30 In fact, in food chemistry, various techniques of drying the food substances are compared using NIR technology, because it is an accepted reference standard for assessing water content. Our primary interest in NIR, similar to other medical researchers, has been its capacity to assess oxygenation and blood volume in tissue. Our collaborative work in the area of NIR spectroscopy represents the fusion of interested clinicians and spectroscopists. Through this collaboration, NIR's capacity to measure water content was recognized as a practical tool in medicine. Advances in edema pathophysiology have been limited, because there are no validated clinical noninvasive tools. The majority of accurate and accepted techniques to assess edema are invasive. Wet to dry measures require a sample of tissue to be dessicated, lymph flow and protein content require the cannulation of lymphatic vessels, and fluorescent techniques require the injection of tracers.31,–34 All of these modalities are impractical in the clinical environment and are not conducive to repeat measures. Popular noninvasive tools include measurements of body weight changes, volumetry, girth, limb circumference, and electrical measurements. Body weight changes are easy to measure but require a baseline measurement and do not provide information about edema pathophysiology.35 The size and shape of a volumeter make it difficult to measure the entire limb, and it can be difficult to transport because of the large volume of water required to fill the cylinder.36 Volumetry is generally limited to the periphery and cannot be used in patients with open wounds. Limb or girth circumference is more practical in the clinical setting, because it only requires a measuring tape. However, results are affected by the degree of tape tension, width, and position.37 Electrical measurement devices that use skin conductivity or impedance are accepted methods for water determination in skin. Electrical measures do not directly measure water content in skin and are limited, because capacitance relies on the degree of probe contact and the salt content of the skin.38 The strength of NIR lies in its capacity to directly and accurately measure water content from a simple reflectance of light. The spectrum of water has been well elucidated. Water actually dominates the in vivo NIR spectra of viable tissue, which makes it relatively easy to measure.39 In normal skin, the absorbance of NIR light by water is low relative to hemoglobin. However, there are 320,000 water molecules for each hemoglobin molecule, which means the water spectrum overshadows the light attenuation by other chromophores.40 In addition, water absorbs NIR light at specific wavelengths and in proportion to the amount of water that exists in the tissue. In this study, water was extracted at 970 nm, because the NIR devices use a detector that is silicon based. Silicon-based detectors are limited to detect light in the wavelength range of 350 to 1100 nm and, consequently, only the second overtone of water can be used. Studies have been published in the cosmetic dermatology literature using NIR technology to assess the effects of different moisturizers or dehydrating solutions on the skin. NIR successfully differentiated the treatment regimens, but these studies were primarily interested in the hydration of the stratum corneum and not necessarily what is occurring in the deeper tissues.20,22 Kilpatrick et al allowed full-thickness porcine skin to be exposed to various relative humidity situations (100, 75, and 11% relative humidity). Overall, as relative humidity is lowered, there should be less water found in the skin. After 3 days of exposure to the humidity conditions, the water content of the skin was measured with an NIR device. They found that the higher the humidity, the greater the area under the absorbance band (the greater the amount of water in the tissue).41 Stamatas et al used a histamine injection model, which is used by dermatologists to mimic cutaneous edema. In this model, histamine injections are given to human subjects, and the edema reaction becomes noticeable in a dose-dependent fashion. In this study, NIR technology could measure the increasing levels of edema formation as the dose of histamine was increased.24 Our group used a rodent reverse McFarlane flap model to demonstrate the NIR's ability to detect changes in edema. In this model, it has been well described that the proximal portion of the flap closest to the pedicle experiences an early rise in edema vs the distal region that desiccates. NIR technology measured an immediate increase in water up to 12 hours after flap elevation in the proximal zone, which declined back to baseline levels by 48 hours. The distal region experienced a 10% drop in water content after flap elevation, and this level continued to decline until 48 hours or the endpoint of the study.39 Overall, the spectrum of water has been so well elucidated that there is no debate over the fact that the 970-nm region represents an OH stretch and, consequently, a measurement of water content. The ability of a noninvasive technology to assess edema has many applications in medicine. Specifically, the ability to measure water (edema) would enable an understanding of the pathophysiology of burn wound edema by its ability to track changes in water content over time. It could be used to assess end points of resuscitation and prevent an over resusciation of the patient and the complications associated with “fluid creep.”42,43 Crookes et al5 have been successful at determining the end points of resuscitation in trauma patients with NIR devices. End points are important in burn resuscitation but, more importantly, the debate continues about the usage of hypertonic saline, albumin, and other regimens to control edema formation and, at the same time, ensure adequate perfusion of the end organs.44,45 Finally, controlling edema in the chronic wound during rehabilitation is important in the functional recovery of the patient.36 However, it is difficult to assess treatment regimens when there is no gold standard for the noninvasive measurement of water content. A device that can measure edema would allow us to objectively evaluate many of the tools used to treat edema and determine the ones that are efficacious. The ability to assess end points of resuscitation, the type of resuscitation regimen, and a proper assessment of edema treatments has applications beyond the field of burns. In this study, NIR spectroscopy documented changes that occur between a burn wound and a healthy unburned region based on water content alone. The control sites or healthy unburned regions, when compared, showed no differences in water content at any of the detector positions. Eleven healthy unburned subjects were used to determine baseline levels of water content. Mean water content was lower in normal unburned patients than that measured in the local control sites of a burn patient. This suggests that the area surrounding the burn region also experiences the local effects of the burn wound, even in small TBSA injuries. Clinically, there was no noticeable edema at the control sites during the study period, which indicates that NIR point spectroscopy can detect changes in water content or edema that are not visible with the naked eye. This finding is consistent with our previous work using NIR to assess hydration in a rodent reverse McFarlane flap model. NIR technology was able to demonstrate these changes in the flap with accuracy as early as 5 minutes after surgery but did not become clinically apparent for 12 hours.39 Most studies performed to date have compared partial-thickness injuries with full-thickness injuries with respect to edema formation and resorption. It is well documented that edema forms more rapidly in a partial-thickness injury compared with the full-thickness burn wounds, and peak edema tends to reach higher levels.17 However, little is known about the differences that may exist between a superficial and a deep partial-thickness injury. In this study, both burn types show high levels of water, but the deep partial-thickness wounds actually showed a 23% increase in water concentration compared with 18% in superficial partial-thickness burn wounds. The fact that superficial partial-thickness burns had less water than deep partial-thickness burns might suggest that superficial burns start the resorption process earlier or do not accumulate the same amount of edema as their deep counterparts at this time point. This is secondary to an intact lymphatic system that can resorb the accumulated edema fluid more rapidly. This finding is consistent with the literature, because full-thickness injuries do not resorb edema fluid as quickly with high levels of edema remaining at 48 hours, and 25% of the edema still remain 1 week after injury.17 Deep partial-thickness burn wounds seem to behave in the same manner with a limited capacity to resorb edema fluid quickly. Water content in the burn wound varied depending on the detector position. The detectors are organized strategically to collect transmitted light from certain regions of the skin and subcutaneous tissue. Detectors 1 and 2 are the superficial and deep dermal detectors, with detector 3 as the subcutaneous tissue detector. Overall, the superficial detector showed less water content (15%) compared with the deeper tissue detectors (23%). This suggests that a greater amount of edema forms in the subcutaneous tissue, when compared with the dermis. Papp et al46 used the dielectric constant to show in a porcine burn model that water content was increased in the subcutaneous fat over the other skin layers and compared with preburn levels. The greatest increase in subcutaneous water content was found in the partial-thickness injuries compared with the superficial- or full-thickness burns. Therefore, the increase in water concentration in the subcutaneous layer may be an important differentiating feature of burn depth. This study represents our preliminary clinical experience with the NIR technology. There are several limitations of this study. The small sample population samples size reflects the nature of a pilot study. Our aim was to prove or disprove that NIR spectroscopy has potential as a noninvasive measure of edema in a clinical environment. Large TBSA burns were excluded, because they are resuscitated with varying levels of fluids, and this would have had an impact on the amount of edema accumulation. Differences in edema formation could have then been attributed to the varying levels of fluid given and would have added a confounding variable. In this study, we wanted to establish baseline results in a nonfluid resuscitated patient population before adding variables into the data processing. Data were collected from the burn wounds and local controls at one time point, 48 hours after burn injury. This time point was chosen based on the referral patterns to our centre for small TBSA injuries, and, also, because at 48 hours, burn patients have reached their peak edema levels and should be in the plateau or the slow resorption phase. It is well known that edema formation is affected by time, burn depth, fluid resuscitation type, and volume, and our future work in this area will investigate these variables. The study goal was to prove that NIR technology is capable of measuring water concentration and, therefore, edema. An additional finding from this study is the fact that edema levels could be used to differentiate partial-thickness injuries. This adds strength to our hypothesis that water content is an important variable when assessing burn depth using NIR spectroscopy and should be used in conjunction with oxyhemoglobin and deoxyhemoglobin variables. Future support for this statement comes from our early porcine burn studies, where a multivariate analysis using the three variables, water, oxyhemoglobin, and deoxyhemoglobin, dramatically improved the robustness of the NIR assessment of depth.47 A noninvasive monitor of edema is instrumental in improving our knowledge of burn edema pathophysiology. Without this knowledge, it is difficult to monitor the effects of current or new therapeutics, thereby limiting potential advances in this area. NIR holds promise as a new noninvasive, portable clinical tool to quantify edema in vivo. A tool that has the capacity to measure edema possesses medical applications that extend well beyond the field of burn wound physiology. Supported by the Physicians' Services Incorporated Foundation grant. REFERENCES 1. Sowa MG, Leonardi L, Payette JR, Cross KM, Gomez M, Fish JS Classification of burn injuries using near-infrared spectroscopy. J Biomed Opt  2006; 11: 054002. Google Scholar CrossRef Search ADS PubMed  2. Cross KM, Leonardi L, Payette JR, et al.   Clinical utilization of near-infrared spectroscopy devices for burn depth assessment. Wound Repair Regen  2007; 15: 332– 40. Google Scholar CrossRef Search ADS PubMed  3. Leonardi L, Sowa MG, Payette JR, Mantsch HH Near-infrared spectroscopy and imaging: a new approach to assess burn injuries. Am Clin Lab  2000; 19: 20– 2. Google Scholar PubMed  4. Dansby W, Purdue G, Hunt J, et al.   Aerosolization of methicillin-resistant Staphylococcus aureus during an epidemic in a burn intensive care unit. J Burn Care Res  2008; 29: 331– 7. Google Scholar CrossRef Search ADS PubMed  5. Crookes BA, Cohn SM, Bloch S, et al.   Can near-infrared spectroscopy identify the severity of shock in trauma patients? J Trauma  2005; 58: 806– 13. Google Scholar CrossRef Search ADS PubMed  6. Crookes BA, Cohn SM, Burton EA, Nelson J, Proctor KG Noninvasive muscle oxygenation to guide fluid resuscitation after traumatic shock. Surgery  2004; 135: 662– 70. Google Scholar CrossRef Search ADS PubMed  7. Cohn SM, Nathens AB, Moore FA, et al.   Tissue oxygen saturation predicts the development of organ dysfunction during traumatic shock resuscitation. J Trauma  2007; 62: 44– 54. Google Scholar CrossRef Search ADS PubMed  8. Aslin RN, Mehler J Near-infrared spectroscopy for functional studies of brain activity in human infants: promise, prospects, and challenges. J Biomed Opt  2005; 10: 11009. Google Scholar CrossRef Search ADS PubMed  9. Pollard V, Prough DS, DeMelo AE, Deyo DJ, Uchida T, Stoddart HF Validation in volunteers of a near-infrared spectroscope for monitoring brain oxygenation in vivo. Anesth Analg  1996; 82: 269– 77. Google Scholar PubMed  10. Kirkpatrick PJ, Smielewski P, Czosnyka M, Menon DK, Pickard JD Near-infrared spectroscopy use in patients with head injury. J Neurosurg  1995; 83: 963– 70. Google Scholar CrossRef Search ADS PubMed  11. Ciurczak DBaE Handbook of near infrared analysis. 2nd ed.  New York: Marcel Dekker, Inc; 2001. 12. Collins SP, Mielniczuk LM, Whittingham HA, Boseley ME, Schramm DR, Storrow AB The use of noninvasive ventilation in emergency department patients with acute cardiogenic pulmonary edema: a systematic review. Ann Emerg Med  2006; 48: 260– 9, 269.e1. Google Scholar CrossRef Search ADS PubMed  13. Ayata C, Ropper AH Ischaemic brain oedema. J Clin Neurosci  2002; 9: 113– 24. Google Scholar CrossRef Search ADS PubMed  14. Walker J, Criddle LM. Pathophysiology and management of abdominal compartment syndrome. Am J Crit Care 2003;12:367–71, quiz 72–3. 15. Honnor A Classification, aetiology and nursing management of lymphoedema. Br J Nurs  2008; 17: 576– 86. Google Scholar CrossRef Search ADS PubMed  16. Pain SJ, Purushotham AD Lymphoedema following surgery for breast cancer. Br J Surg  2000; 87: 1128– 41. Google Scholar CrossRef Search ADS PubMed  17. Demling RH The burn edema process: current concepts. J Burn Care Rehabil  2005; 26: 207– 27. Google Scholar CrossRef Search ADS PubMed  18. Attas EM, Sowa MG, Posthumus TB, Schattka BJ, Mantsch HH, Zhang SL Skin hydration images from near-infrared reflectance spectra. Am Clin Lab  2002; 21: 32– 6. Google Scholar PubMed  19. Attas EM, Sowa MG, Posthumus TB, Schattka BJ, Mantsch HH, Zhang SL Near-IR spectroscopic imaging for skin hydration: the long and the short of it. Biopolymers  2002; 67: 96– 106. Google Scholar CrossRef Search ADS PubMed  20. de Rigal J, Losch J, Bazin R, et al.   Near-infrared spectroscopy: a new approach to the characterization of dry skin. J Soc Cosmet Chem  1993; 44: 197. 21. Martin K In vivo measurements of water in skin by near-infrared reflectance. Appl Spectrosc  1998; 52: 1001. Google Scholar CrossRef Search ADS   22. Walling PL, Dabney JM Moisture in the skin by near-infrared reflectance spectroscopy. J Soc Cosmet Chem  1989; 40: 151. 23. Zhang SL, Meyers CL, Subramanyan K, Hancewicz TM Near infrared imaging for measuring and visualizing skin hydration. A comparison with visual assessment and electrical methods. J Biomed Opt  2005; 10: 031107. Google Scholar CrossRef Search ADS PubMed  24. Stamatas GN, Southall M, Kollias N In vivo monitoring of cutaneous edema using spectral imaging in the visible and near infrared. J Invest Dermatol  2006; 126: 1753– 60. Google Scholar CrossRef Search ADS PubMed  25. Kramer GC, Lund T, Herndon D Pathophysiology of burn shock and burn edema. Herndon D Total burn care.  London: Saunders; 2002 78– 85. 26. Lee RC, Astumian RD The physicochemical basis for thermal and non-thermal ‘burn’ injuries. Burns  1996; 22: 509– 19. Google Scholar CrossRef Search ADS PubMed  27. Isengard HD Water content, one of the most important properties of food. Food Control  2001; 12: 395– 400. Google Scholar CrossRef Search ADS   28. Mouazen AM, Karoui R, De Baerdemaeker J, Ramon H Characterization of soil water content using measured visible and near infrared spectra. Soil Sci Soc Am J  2006; 70: 1295– 302. Google Scholar CrossRef Search ADS   29. Vesela A, Barros AS, Synytsya A, Delgadillo I, Copikova J, Coimbra MA Infrared spectroscopy and outer product analysis for quantification of fat, nitrogen, and moisture of cocoa powder. Anal Chim Acta  2007; 601: 77– 86. Google Scholar CrossRef Search ADS PubMed  30. Reh C, Bhat SN, Berrut S Determination of water content in powdered milk. Food Chemistry  2004; 86: 457– 64. Google Scholar CrossRef Search ADS   31. Shimizu S, Tanaka H, Sakaki S, Yukioka T, Matsuda H, Shimazaki S Burn depth affects dermal interstitial fluid pressure, free radical production, and serum histamine levels in rats. J Trauma  2002; 52: 683– 7. Google Scholar PubMed  32. Mowlavi A, Neumeister MW, Wilhelmi BJ, Song YH, Suchy H, Russell RC Local hypothermia during early reperfusion protects skeletal muscle from ischemia-reperfusion injury. Plast Reconstr Surg  2003; 111: 242– 50. Google Scholar CrossRef Search ADS PubMed  33. Hedenstierna G, Lattuada M Lymphatics and lymph in acute lung injury. Curr Opin Crit Care  2008; 14: 31– 6. Google Scholar CrossRef Search ADS PubMed  34. Zaugg-Vesti B, Dorffler-Melly J, Spiegel M, Wen S, Franzeck UK, Bollinger A Lymphatic capillary pressure in patients with primary lymphedema. Microvasc Res  1993; 46: 128– 34. Google Scholar CrossRef Search ADS PubMed  35. Tanaka H, Matsuda T, Miyagantani Y, Yukioka T, Matsuda H, Shimazaki S Reduction of resuscitation fluid volumes in severely burned patients using ascorbic acid administration: a randomized, prospective study. Arch Surg  2000; 135: 326– 31. Google Scholar CrossRef Search ADS PubMed  36. Karges JR, Mark BE, Stikeleather SJ, Worrell TW Concurrent validity of upper-extremity volume estimates: comparison of calculated volume derived from girth measurements and water displacement volume. Phys Ther  2003; 83: 134– 45. Google Scholar PubMed  37. Tewari N, Gill PG, Bochner MA, Kollias J Comparison of volume displacement versus circumferential arm measurements for lymphoedema: implications for the SNAC trial. ANZ J Surg  2008; 78: 889– 93. Google Scholar CrossRef Search ADS PubMed  38. Arimoto H, Egawa M Non-contact skin moisture measurement based on near-infrared spectroscopy. Appl Spectrosc  2004; 58: 1439– 46. Google Scholar CrossRef Search ADS PubMed  39. Sowa MG, Payette JR, Mantsch HH Near-infrared spectroscopic assessment of tissue hydration following surgery. J Surg Res  1999; 86: 62– 9. Google Scholar CrossRef Search ADS PubMed  40. Attas M, Hewko M, Payette J, Posthumus T, Sowa M, Mantsch H Visualization of cutaneous hemoglobin oxygenation and skin hydration using near-infrared spectroscopic imaging. Skin Res Technol  2001; 7: 238– 45. Google Scholar CrossRef Search ADS PubMed  41. Kilpatrick-Liverman L, Kazmi P, Wolff E, Polefka TG The use of near-infrared spectroscopy in skin care applications. Skin Res Technol  2006; 12: 162– 9. Google Scholar CrossRef Search ADS PubMed  42. Cartotto RC, Innes M, Musgrave MA, Gomez M, Cooper AB How well does the Parkland formula estimate actual fluid resuscitation volumes? J Burn Care Rehabil  2002; 23: 258– 65. Google Scholar CrossRef Search ADS PubMed  43. Pruitt BA Jr Protection from excessive resuscitation: “pushing the pendulum back.”. J Trauma  2000; 49: 567– 8. Google Scholar CrossRef Search ADS PubMed  44. Oda J, Yamashita K, Inoue T, et al.   Resuscitation fluid volume and abdominal compartment syndrome in patients with major burns. Burns  2006; 32: 151– 4. Google Scholar CrossRef Search ADS PubMed  45. O'Mara MS, Slater H, Goldfarb IW, Caushaj PF A prospective, randomized evaluation of intra-abdominal pressures with crystalloid and colloid resuscitation in burn patients. J Trauma  2005; 58: 1011– 8. Google Scholar CrossRef Search ADS PubMed  46. Papp A, Lahtinen T, Harma M, Nuutinen J, Uusaro A, Alhava E Dielectric measurement in experimental burns: a new tool for burn depth determination? Plast Reconstr Surg  2006; 117: 889– 98. Google Scholar CrossRef Search ADS PubMed  47. Sowa MG, Leonardi L, Payette JR, Fish JS, Mantsch HH Near infrared spectroscopic assessment of hemodynamic changes in the early post-burn period. Burns  2001; 27: 241– 9. Google Scholar CrossRef Search ADS PubMed  Copyright © 2009 by the American Burn Association
TI - Noninvasive Measurement of Edema in Partial Thickness Burn Wounds
JF - Journal of Burn Care & Research
DO - 10.1097/BCR.0b013e3181b485e9
DA - 2009-09-01
UR - https://www.deepdyve.com/lp/oxford-university-press/noninvasive-measurement-of-edema-in-partial-thickness-burn-wounds-iLi6Q5fHbZ
SP - 807
EP - 817
VL - 30
IS - 5
DP - DeepDyve
ER -