Quantitative assessment of autonomic dysreflexia with ...

Quantitative assessment of autonomic dysreflexia with combined spectroscopic and perfusion probes Jessica C. Ramella-Roman1 , Allison Pfefer1 , Joseph Hidler2 1

The Catholic University of America, 620 Michigan Ave., N.E.,Washington, DC 2 The National Rehabilitation Hospital, 102 Irving St. N.W., Washington, DC ABSTRACT

Autonomic Dysreflexia (AD) is an uncontrolled response of sympathetic output occurring in individuals with an injury at the sixth thoracic (T6) neurologic level. Any noxious stimulus below the injury level can trigger an AD episode. Progression of an AD attack can result in severe vasoconstriction below the injury level. Skin oxygenation can decrease up to 40% during an AD event. We present a quantitative and non-invasive method of assessing the progression of an AD event by measuring patient’s skin oxygen levels and blood flow using a fiber optic based system. Keywords: Spectroscopy, autonomic dysreflexia, Laser doppler

1. INTRODUCTION Autonomic Dysreflexia (AD) is a severe condition of sympathetic output that usually occurs in patients suffering from spinal cord injury at or above the sixth thoracic (T6) neurologic level. Autonomic Dysreflexia can be triggered by any noxious stimulation that occurs below the level of injury such as a full bladder, an ingrown toenail, or a pressure sore. Managing AD properly can prevent severe symptoms both above and below the level of injury. Due to the disruption of the sympathetic pathways, splanchnic and distal peripheral vasoconstriction will persevere below the lesion level [1]. Flushing and sweating of the head and neck, mucous membrane congestion, conjunctivitis, blurred vision, and lid retraction are some of the symptoms occurring above the level of injury. Pallor with cold peripheries, pilomotor erections, intense contraction of bladder and bowel, increased spasticity, and penile erection are other symptoms that can be observed below the lesion level [2,3]. Removing the stimulus that caused AD is the only way to stop the episode. The autonomic nervous system through parasympathetic and the sympathetic nervous system maintains the body’s homeostasis. Parasympathetic and the sympathetic nervous system are located in two different part of central nervous system, and they have a complementary and opposite roles. The sympathetic nervous system is associated with the flight or fight response. A sensory impulse will be generated as a result of stimulation below the level of the lesion in an individual with SCI at or above the T6 level. This sensory impulse produces a generalized sympathetic response that results in vasoconstriction below the level of injury. Due to the spinal cord injury, the parasympathetic nervous system can not counteract these effects. As a result the parasympathetic nervous system tries to maintain homeostasis by slowing down the heart rate, causing vasodilation and bradycardia above the injury level. Headache, flushing and sweating in the head and neck region are thought to be direct symptoms of the vasodilation resulting from the excessive parasympathic output. Generalized sweating has also been observed below the physiological level of the lesion in most complete sensory and motor paralysis and in some incomplete lesions [1]. The two nervous systems will be isolated from each other due to the blocked pathway. This allows all symptoms to remain unaffected until the stimulus is removed. Removing the painful stimulus that triggered AD event is the only way to end this episode. However, the individual will experience elevating levels of symptoms if no action is taken. We believe that the circulatory dysfunction caused by AD, including hypoxia, ischemia and increased perspiration, can negatively impact the health of the skin contributing to the formation of skin ulcers. The National Pressure Ulcer Advisory Panel defines Stage (I) pressure ulcer as intact skin with non-blanchable redness of a Further author information: (Send correspondence to Ramella-Roman J.C.) R.R.J.C.: E-mail: [email protected], Telephone: 1 202 319 6247

Advanced Biomedical and Clinical Diagnostic Systems VII, edited by Anita Mahadevan-Jansen, Tuan Vo-Dinh, Warren S. Grundfest, Proc. of SPIE Vol. 7169, 716916 © 2009 SPIE · CCC code: 1605-7422/09/$18 · doi: 10.1117/12.809000 Proc. of SPIE Vol. 7169 716916-1

contained area usually over a bony prominence [4]. In a patient suffering from multiple episodes of AD an area of nonblanchable redness could occur as a result of repetitive process of reactive hyperemia. Previous study showed that oxygen values decrease dramatically following an AD episode and surpass normal levels in the short time after the bladder was drained [5].

2. MATERIAL AND METHODS Measurement of skin perfusion and oxygenation in SCI individuals undergoing AD events were obtained with a system that combined Laser Doppler flowmetry (LD) and reflectance spectroscopy (R) shown in Fig.1. Three different locations in the individual skin were monitored, one above and two below the level of injury. The measurement above the level of injury (on the patient forearm, one LD and one R measurement) was used as a reference since nothing is expected to change in hemodynamics at that location. The two measurements below the level of injury were obtained on the left hip (one LD and one R measurement) and right hip (one LD and two R measurement). The spectral reflectance measurement was accomplished with a spectrophotometer (Ocean Optics, Dunedin, FL), and a tungsten halogen lamp (Ocean Optics, Dunedin, FL), a Laser Doppler system (Moor Instruments Ltd., UK) was used for the perfusion measurement. In the clinical setting we used three different types of fiber probes: LD factory-made probes (Moor Instruments Ltd., UK), custom made reflectance spectroscopy fiber probes, and a custom made combined spectral and doppler probe. All devices and the controlling laptop were assembled on a cart for the purpose of maneuverability inside the hospital during the clinical trial.

Figure 1. Experimental apparatus

2.1 Custom Probes Two types of fiber optic probes were fabricated for this study. The first probe was made with two multimode 600μm fibers (Thorlabs, Newton, New Jersey, 0.39 NA), one source and one detector, 2 meters long with an SMA-905 adapter at one side for connection to a spectrophotometer. An aluminum coated 1mm right angle prism (Tower Optical Corporation, Boynton Beach, FL) was attached to the polished side of each fiber using a UV curing index matched adhesive (Norland Products Inc, Cranbury, NJ). The fibers and prisms were then positioned inside a machined Delrin disk (2 mm thick, 25mm diameter). This geometry allowed a redirection of light to 90 degrees from the fiber axis. The fibers distance center to center was 2.5mm as shown in Fig. 2. A small amount of clear epoxy was applied to secure the fiber inside the Delrin support. The top surface of the probe support was painted black to block light penetration from outside sources. The second probe was designed for the purpose of measuring both reflectance and perfusion in nearby regions of the patient skin. The probe consisted of three multimode 600μm fibers, (one source and two detectors), for

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R measurements and two multimode 200μm fibers for LD measurement as shown in Fig. 3. We will refer to this probe as the combined probe. The 600μm fibers were combined with the same 1mm prisms as previously described, while the flexible 200 μm fibers were bent close to 90 degree to channel light directly to the skin surface. A Delrin disk (dimeter 25.5mm, thickness 10mm) was used to support all the fibers, a small amount of epoxy was used to keep the fibers in place. The top surface of the probe was painted black. A pressure sensor (Trossen Robotics, Westchester, IL) was attached to the top of the combined probe to monitor applied pressure to the skin. The sensor was connected to an interface kit (Trossen Robotics, Westchester, IL) to obtain a digital reading of the applied pressure. An algorithm described by Kollias et al. [7] was used to analyze the data. The algorithm uses the curve of absorbance of skin, which is simply the logarithm of the ratio of the skin diffused reflectance to a reflectance standard (Spectralon standard 99% reflectance). The total absorbance curve of skin is corrected for melanin absorption by subtracting its contribution from the general data. Skin pigmentation is approximated as the slope of a fitted straight line between the values of absorbance at 620 and 720 nm, the absorbance curve of melanin decreasing monotonically between 600 and 750 nm. Oxygen saturation is calculated by using tabulated absorption curves of oxygenated and deoxygenated hemoglobin to fit the experimental data in the range 550 to 580 nm. In this range both curves exhibit local maxima [8].


3. RESULTS All fiber probes were tested on able bodies individuals before the start of the clinical trial. In order to simulate the AD event and its impact on the skin a pressure cuff was used to block blood flow to a volunteer forearm for several minutes. The probe was placed on the individual skin and a transparent gel was added at the skinprobe interface for index matching. The test length was 10 minutes. During the first one and a half minute we measured baseline values of blood flow and skin oxygenation. The pressure cuff was then inflated for the duration of two minutes. Finally the pressure cuff was released and oxygenated blood was allowed to return to the area. Contemporaneous measurements of perfusion and oxygenation were conducted, probe pressure on the arm and skin temperature were also continuously monitored but are not shown here.

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Figure 4 shows the result of the test obtained with the combined probe. Blood flow dropped abruptly right after the pressure cuff was inflated. The oxygen level seemed to respond differently and decreased more gradually nevertheless a minimum was reached for both measurements. The skin oxygen level rose after pressure was released returning to normal levels, the LD measurement on the other hand overshoot (close to minute four) possibly due to pressure built-up in the local vasculature. This test showed that the probe and instrumentation were able to characterize an ischemic event in real time. A clinical trial is being conducted at the National Rehabilitation Hospital in Washington DC. All subjects are required to sign an informed consent approved by the Institutional Review Boards of Medstar Research Institute and The Catholic University of America. The inclusion criteria for this study are sensory and motor complete SCI at or above T6 and at least one year post-injury so that Autonomic Dysreflexia symptoms have stabilized. All subjects are transferred onto an adjustable chair with a high back and foot rest and are seated on a foam cushion. Once positioned a clinician injects up to 500 ml of saline solution into the patient bladder using a foley catheter, in increments of 100 ml. If the subjects vital signs are normal yet no AD has been detected, another 100 ml of fluid is added. Total volume is limited to 500 ml to exclude bladder injury. It should be noted that this volume is routinely used in urodynamics studies with limited risk to the subject. It should also be stressed that throughout the procedure, blood pressure, heart rate, and overall subject appearance are closely monitored. If at any time the systolic blood pressure exceeds 160 mmHg, the diastolic pressure exceeds 100 mm Hg, or if the clinician does not feel comfortable with the subjects condition, the bladder is drained and the experiment is stopped. Since the symptoms of AD dissipates rapidly with the drainage of the full bladder, there is little risk to the subject. Figure 5 shows the results for one individual. The LD and SO2 measurement on the right hip (location 1, LD1) show a typical decrease in value as the AD event is reported. The measurement on the patient forearm


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Figure 5. Combined pulse oximetry and laser doppler measurement for an individual undergoing an AD event. The solid line follows the LD measurement above the level of injury, the dot-dashed line follows the LD measurement below the level of injury

LD2 and SO2 did not show a significant decrease in values, but it is should be noted that perfusion levels on the forearm were significantly lower than the one observed on the hip. The patient bladder was filled with 350 ml of saline before first symptoms of AD were reported (around minute 9). Due to the patient fast increasing blood pressure we decided to interrupt the measurement shortly thereafter and the patient bladder was drained completely at time = 12 min. Both the LD and SO2 measurement show that the patient is slowly recovering to normal values. Several deviation in the signal can be seen in Fig. 5 and are due to movement artifacts. We are considering filtering schemes to eliminate this low frequency noise. The results, albeit preliminary, are in agreement with previously reported studies on skin oxygenation in SCI individuals [5].

4. CONCLUSIONS Many individuals with spinal cord injury suffer from autonomic dysreflexia. This event can be triggered by a full bladder, an ingrown toenail, or a pressure sore. As a result of this event, headache, flushing, and sweating in the head and neck region can occur. We hypothesize that the continuous ischemic and hyperemic events caused by AD have a negative impact on skin tissue and could lead over time to pressure ulcer. Unfortunately there have not been enough studies to explore the long-term effects of AD events. We have constructed a system based on fiber optic probes to monitor blood flow and oxygen saturation in the skin of SCI individuals undergoing AD. We have shown that the probes can accurately monitor ischemia and hyperemia in real time and we are currently conducting a clinical trial at the National Rehabilitation Hospital to show that AD causes severe de-oxigenation and loss of perfusion in the skin of SCI individuals below the level of injury.

5. ACKNOWLEDGEMENTS This work was supported by the Christopher Reeve Foundation. The authors thank Afshin Nabili for his support during fibers fabrication.


6. REFERENCES 1. L.S. Kewalramani, “Autonomic Dysreflexia in Traumatic myelopathy,” American Journal of Physical Medicine. 59. 1-21 (1980). 2. I.S. Shergill, M. Arya, R. Hamid, J. Khastgir, H.R.H. Patel, P.J.R. Shah, “The importance of autonomic dysreflexia to the urologist,” British Journal of Urology. 93, 923-926 (2003). 3. J.Z. Montgomerie, “Infections in Patients with Spinal Cord Injuries,” Clinical Infectious Diseases. 25. 1285-92 (1997). 4. J. Black, M. Baharestani, J. Cuddigan, B. Dorner, L. Edsberg, D. Langemo, M. E. Posthauer, C. Ratliff, G. Taler, “National Pressure Ulcer Advisory Panel’s Updated Pressure Ulcer Staging System,” Dermatology Nursing. 19. (2007). 5. J.C. Ramella-Roman, J.M. Hidler, “A fiber optic probe measurement of an autonomic dysreflexia event on SCI patients,” Optical Fibers and Sensors for Medical Diagnostics and Treatment Applications VIII. 685202-05 (2008). 6. Fernando Morales, “Improving the clinical applicability of laser Doppler perfusion monitoring” (PhD dissertation, Rijksuniversiteit Groningen, 13-111, (2005) 7. N. Kollias, AH Baqer, “Quantitative assessment of UV-induced pigmentation and erythema,” Photodermatol; 5, 53-60, (1988) 8. S. Takatani and M. D. Graham, “Theoretical analysis of diffuse reflectance from a two-layer tissue model,” IEEE Trans. Biomed. Eng., BME-26, 656-664, (1987)
