Hyperbaric Oxygen Therapy and Radiation-Induced Injuries

Abstract

Initial clinical uses of hyperbaric oxygen (HBO₂) capitalized upon physical effects to drive offending gases back into solution and deliver more oxygen to tissues in early treatments of decompression sickness. HBO₂ has a myriad of other effects, including stimulating angiogenesis and new cellular in growth for healing.

HBO₂ Applied to Patients with Osteoradionecrosis of the Mandible

As incremental improvements in head and neck cancers improved survival with better surgical techniques for more complete tumor extirpation plus better radiation for enhanced local control and even further adjuvant therapies that increased long term survival, patients began living long enough to suffer all the sequelae of osteoradionecrosis (ORN) of the mandible. Patients who had otherwise been cured of their original cancer now suffered ever worsening dentition, including loosening and loss of teeth, and even pathological jaw fractures. These seriously impacted their quality of life for eating, speech, social isolation with open draining sockets, problematic and malodorous wounds and exposed bone and pain.^1,2 As more of these challenging patients presented, it was easy to assume that the exposed bone and soft tissue problems were related to chronic colonization and then resultant infections due to the inherently high bacterial counts in the mouth. Although increasingly stronger antibiotic regimens and surgical dental and bone stabilization protocols were instituted many patients still suffered less than optimal outcomes thought to be related to variants of osteomyelitis of the mandible.³ At the same time, HBO₂ was accumulating data that high oxygen tensions were toxic to certain bacteria, such as clostridia species, and might also have other cellular effects for better healing in ORN.⁴

Real HBO₂ Effects Irradiated Tissue worked out in ORN and then in other Tissues

This led to an oral surgeon, Dr. Robert E Marx, and others to study if HBO₂ could synergistically improve antibiotic control of surgical complications in ORN.^5,6 Fortunately, in the effort to study the bacterial loads, the pathological bone specimens were carefully analyzed in the course of these trials that included prospective, randomized arms both with and without HBO₂. Although it was expected that those receiving HBO₂ would have lower bacterial counts, lower amounts of bacteria in the bone, and less culturing of bacteria causing problems for healing, there was a different serendipitous finding: the bone samples in the HBO₂ arms all had increased densities of new blood vessels and in growth of cells that were not present before treatment.^{7, 8, 9, 10} HBO₂ was having an effect on infection and bone breakdown from stimulating neo-angiogenesis in the bone which allowed the bone to tolerate further surgical manipulation and heal. This was and continues to be a paradigm shift in patient’s care after medical irradiation.^{11, 12} A process, radiation-induced tissue fibrosis and its hypo-vascularity, was being offset by the stimulatory effects of HBO₂.^{13, 14}

By stimulating new blood vessel and cellular in growth, this increased blood flow to allow the bone and soft tissues to heal. This gave head, neck, and oral surgeons increased capabilities and lower incidences of complications for patients. These neo-angiogenesis effects have later been better demonstrated with an array of cellular and cytokine effects and form a more modern way of looking at how HBO₂ treats not only ORN of the mandible,^15,16 but also for laryngeal and soft tissue necrosis in the head and neck^17,18 chest wall necrosis and post breast cancer irradiation syndromes,¹⁹ radiation cystitis²⁰ radiation proctitis, rads enteritis, and pelvis floor organs including the vagina²¹ and neural tissues and the brain.^22,23

All of these radiation injury effects can be have HBO₂ to augment therapeutic responses for the patient. The effects of radiation can be early or delayed, but should a patient with skin, soft tissue including intra-oral or other mucosal surfaces (urogenital or GI)²⁴, bony, or neural tissue are symptomatically changing after irradiation, then adjunctive HBO₂ can be considered.²⁵ In many ways the radiation induced hypovascularity is similar to the diabetes mellitus induced hypovascularity where HBO₂ has also been shown to be beneficial where the cycling of hypoxia (while in the HBO₂ chamber) and then the slow decay back to baseline hypoxia after treatment is stimulatory for neoangiogenesis.²⁶

With the advent of ever larger data registries, more applications of HBO₂ for radiation-induced changes are accumulating. As in other non-healing applications for adjunctive HBO₂ better data will optimize practice guidelines, documented efficacies and also allay some safety concerns as many post irradiated patients may be at risk for tumor recurrence regardless of any HBO₂ offered. Although to date, there is no accumulated evidence for increased cancer recurrences with HBO₂.^27,28 In fact, especially for head and neck cancers, further tracking of recurrences is demonstrating specific differences in tumor biology that predict cancer re-growth such that better HBO₂ tracking may contribute to finding patients at risk for cancer recurrences.²⁹

Conclusions

Irradiated tissue responses well delineated in hyperbaric ORN studies are a more modern conceptualization of HBO₂ effects and potential value to patients. As ever increasing sophistication of basic science capabilities to delineate cellular and tissue responses occur, HBO₂ has been found to have effects beyond oxygenation. As HBO₂ increases tissue oxygenation and improves blood flow, it also effects cellular responses for healing.³⁰ However interesting these basic science mechanism are to consider, modern evidence based recommendations are also based upon clinical evidence and this is where better data registries will make an impact. The cumulative patient and tissue improvements seen in ORN and other post irradiation changes demonstrate the additional, adjunctive value of HBO₂ in other similarly damaged tissue states.

Figure 1.

Healed to clean dry scabs, hyperbaric sequence completed at 40 treatments.