The Dosage of Hyperbaric Oxygen in Chronic Brain Injury
Paul G. Harch M.D.
The concept of dosage of hyperbaric oxygen therapy (HBOT) derives from the definition of HBOT as a drug. Using the broad definition of HBOT by Harch and Neubauer (1), HBOT is the use of greater than ambient pressure oxygen as a drug to treat basic pathophysiologic processes/states and their diseases. Drug dosage of HBOT, therefore, is a function of baseline or reference ambient pressure, depth of pressurization, duration, frequency, air breaks, surface interval, number of treatments, idiosyncratic genetic patient factors, and time to intervention in the disease process which determines the pathological targets. All of these factors cause HBOT to be a narrow-window drug in chronic brain injury similar to digoxin and coumadin: too litfie maybe ineffective and too much can be toxic. In addition, oxygen is a respiratory metabolite: ;too little has serious metabolic consequences and too much can cause metabolic fatigue. Determining the proper dosage in a given patient with a specific or multiple diseases can be difficult. Ultimately, one wants the best dosage that improves the patient while doing the least harm.
HBOT has both acute and chronic effects (2). This paper will address only the chronic effects. Chronic effects of HBOT include fibroblast stimulation, collagen deposition, anglogenesis, epithelialization, and bone remodeling. This is most evident in shallow perfusion gradient wounds such as the classic homogenous wound of external beam radiation. In this animal and human model, Marx (3) has shown that intermittent exposure to HBOT induces the aforementioned chronic trophic effects to cause wound healing. The final level of tissue oxygenation after HBOT is approximately 80% of normal tissue, but the effect is durable for years. The unproven mechanism of the effect is thought to be secondary to transient elevation of tissue oxygen levels that results in a steep oxygen gradient that causes anglogenesis. Since 1995 this effect has been better characterized as signal induction where the drug HBOT, by elevation of tissue oxygen pressures, alone or in combination with other factors, signals the DNA to begin transcription of various gene sequences to mRNA (4,5,6). The mRNA is translated to proteins which cause trophic tissue changes, i.e., wound healing. These mechanisms are thought to be responsible for the HBOT-induced wound healing that is seen in a large variety of chronic non-healing wounds, such as arterial insufficiency, venous insufficiency, diabetic, radiation, sickle cell, vasculitic, and other ulcers.