Ultrasound-Mediated Oxygen Delivery to Lower Extremity Wounds
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Index: WOUNDS. 2012;24(8):201–206.
Abstract: Critical limb ischemia (CLI), an end result of peripheral arterial disease, remains a major clinical challenge. Wound healing in patients with CLI can be difficult due to diminished tissue oxygenation, often leading to recalcitrant ulcers and frequent limb loss. Numerous therapies, including hyperbaric oxygen therapy (HBOT), have been used to correct this regional ischemia, although often with mixed results. This case series investigates the effects of oxygen therapy delivery augmented by low-frequency ultrasound, a device that combines surface acoustic waveform (SAW) low-frequency ultrasound with hyper-oxygenated saline to deliver oxygen to wounds. Participants included 7 patients (7 men, median age 63 years, all with hypertension) with CLI and full-thickness wounds. Baseline therapy PaO2 measurements were taken before therapy, after provision of hyper-oxygenated saline, and after sonification. The device was found to successfully oxygenate the wound beds; PaO2 levels increased by a median of 59.7%, a maximum of 116%, and a median absolute difference peaking at 10.8 mmHg PaO2 (P = 0.018). In conclusion, the treatment increases wound oxygen levels and may be an option in CLI therapy.
Critical limb ischemia (CLI), a condition that results from advanced peripheral arterial disease, retarding oxygen delivery to the affected extremity, is manifested by symptoms including constant lower extremity rest pain or nonhealing ulceration. Approximately 40% of patients with CLI require amputation of the affected limb, resulting in approximately 150,000 amputations in the United States annually.1
Oxygen is involved with several crucial steps of wound healing and is considered the rate-limiting factor of wound improvement. Serving as a nutrient for cell metabolism, phagocytes and other cells of the immune system convert oxygen into reactive oxygen species (ROS) that are then used for wound healing. Moreover, oxygen promotes angiogenesis through inducing vascular endothelial growth factor (VEGF) transcription and myofibroblast production, and functions as a cofactor in collagen synthesis.2
Historically, low-frequency ultrasound (<100 kHz) has been used to increase the rate at which drugs and macromolecules are absorbed through cell membranes and the epidermal stratum corneum. The mechanisms associated with this process are poorly understood, although they are likely due to a combination of cavitation and acoustic streaming.3-5 Furthermore, therapeutic ultrasound has been shown to decrease bacterial resistance to antibiotics, suggesting enhanced permeability of micro-organisms in this setting.6,7
Normal saline solutions exhibit 6 ppm to 8 ppm of dissolved oxygen gas at sea level. By using a sparging technique, which entails the replacement of dissolved nitrogen, gas levels exceeding 24 ppm or more can be demonstrated. This gas replacement, or sparging, technique is defined by Henry’s Law of Partial Pressure.
The purpose of this study was to determine whether a surface acoustic waveform (SAW) low-frequency ultrasound device paired with hyper-oxygenated saline could synergistically deliver oxygen to wounds.
Study population and clinical definitions. Nine patients with leg ulcers were enrolled in this single-center feasibility study conducted over a 2-month period (August 2009 to October 2009) at the Wound Healing and Hyperbaric Medicine Center, Raleigh, NC.