Thursday, June 28
John Feldmeier, DO
"Hyperbaric oxygen and cancer treatment with emphasis on its potential role combined with ketogenic diet and chemotherapy."
At the same time, other researchers have advocated hyperbaric oxygen as a primary treatment for malignant conditions, though the support is limited here. A number of studies done in the late 1950s through the 1970s even on review many years later firmly establish simultaneous hyperbaric oxygen as a radiosensitizer. There are reasons to believe that sequential hyperbaric oxygen followed immediately by can enhance cancer cell kill. The pioneering work by several Japanese authors have reported encouraging results in applying this combined treatment in high-grade brain tumors. More recently, a similar study supported in part by the Baromedical Research Foundation has shown the feasibility of applying these principles to head and neck cancers receiving both chemotherapy and radiation therapy with impressive results and no unexpected toxicities.
There is a strong rationale and a bit of research that also suggest that chemotherapy’s antitumor effects can be enhanced by hyperbaric oxygen as well. Certainly, the logistics of delivering chemotherapy in the hyperbaric chamber are much easier than delivering radiation with HBO2.
In this session, Dr. John Feldmeier will introduce an overview of the above issues. These will include a discussion of the Warburg effect and its implications for combined HBO2 and chemotherapy and HBO2 combined with the ketogenic diet. A brief update will be presented on the status of HBO2 alone and how it effects malignant growth. Other mechanisms by which chemotherapy delivery and tumoricidal effects can likely be enhanced will be considered.
Mr. Richard Clarke will follow with a lecture updating the experience in a multi-center trial using sequential HBO2 and radiation with chemotherapy in advanced head and neck cancer patients.
Dick Clarke, CHT
"Hyperbaric Oxygen Radiation Sensitization of Squamous Cell Carcinomas of the Oropharynx"
This presentation summarizes the first study of hyperbaric oxygen chemo-radiation sensitization for locally advanced squamous cell carcinomas of the oropharynx. It took the form of a Stage I dose escalation trial, designed to determine safety, feasibility and tolerability when hyperbaric oxygen was added to standard care: namely intensity modulated radiation therapy and cisplatinum chemotherapy. The presentation will describe the biological plausibility and physiologic basis for pre-radiation hyperbaric hyperoxia, and the rationale for selection of this tumor type and tumor grade. The hyperbaric dosing regimen, one based upon previous human tumor oxygen response curves, is discussed, and the critical time window for radiation therapy “beam on” from exiting the chamber discussed. Evolution from earlier sensitization studies that employed concurrent hyperbaric oxygen-radiation therapy to the modern sequential approach are described, as well as its inherent advantages. A staging protocol employed to titrate hyperbaric dose against possible acute toxicities is described. Acute toxicities and five-year follow-up results are presented, as is a Stage III study design, in the form of a randomized, sham controlled clinical double-blind trial.
Stephen Thom, MD
"Hyperbaric Oxygen Therapy Cell Signaling & Mechanisms of Action"
This lecture will summarize current knowledge on mechanisms of action for hyperbaric oxygen (HBO2) therapy. Information will include findings from peer-reviewed publications involving both animal and human studies. It will emphasize data from human investigations, with a focus on those actions most relevant to clinical HBO2 indications.
Friday, June 29
Caroline Fife, MD
"The Hyperbaric Oxygen Therapy Registry and the role of a Qualified Clinical Data Registry in protecting reimbursement"
The field of hyperbaric oxygen therapy and hyperbaric practitioners are under unprecedented scrutiny, with a resulting 50% decrease in HBO2 utilization nationally. Most practitioners are now subject to The Merit Based Incentive Payment System (MIPS), which requires the submission of quality measures. Qualified Clinical Data Registries (QCDRs) can develop specialty-specific quality measures and transmit data to CMS on behalf of clinicians, increasing the opportunity for bonus payments.
The HBOTR, through the USWR, offers specialty registry participation as part of MIPS. Registry participation is possible via automated transmission of Continuity of Care Documents (CCDs) which can enable national benchmarking of many key parameters and can address patient selection bias for other types of registry participation by providing a “denominator” for patients/conditions treated. QCDRs manage identified data and can link to the Medicare data warehouse, facilitating HBO2 cost effectiveness research. Patient-reported questionnaires can be enshrined as quality measures, enabling practitioners to realize a small reimbursement benefit for performing them. Provider scores on specialty-specific quality measures are publicly available via the USWR website linked to “Physician Compare,” a welcome alternative to star ratings derived only from standard (and irrelevant) MIPS measures. Hyperbaric Centers may also benefit from quality measure reporting. The HBOTR leverages current mandatory reporting quality requirements and available electronic health record technology to automate registry participation, an important consideration given the lack of funding for HBO2 research.
The HBOTR has already saved physician payment from a substantial reduction and can be harnessed for clinical research. Since January 2012, data on 27,404 patients has been captured. Among the 62,843 DFUs with data, 9,908 DFUs (15.7%) were treated with HBO2 therapy, although in 2017, the benchmark rate for HBOT was 7.3%, with an average of 28 treatments per patient. There are 2,100 providers who report data to the USWR by transmitting CCDs from their EHR and 688 who submit quality measure data, 300 (43.6%) of whom transmit HBO2 quality measure data.
Jay Buckey, MD
"The hyperbaric medicine registry at Dartmouth"
The value of hyperbaric oxygen is being questioned even for well-established UHMS-approved indications. Although every hyperbaric center treats cases for established indications, the outcomes are not gathered together at a central site, analyzed, and published. As a result, outcome data for hyperbaric oxygen are limited and hard to find. An outcomes registry collects outcomes data from multiple sites consistently, which could allow for more powerful analyses, and more widely accessible results. This talk will describe the outcomes-focused hyperbaric registry currently in use at Dartmouth, and how it could be used to advance the field of hyperbaric medicine.
Judy Rees, MD, PhD
"The role of registries in medicine"
The goal of a disease or treatment registry is to document important data systematically from a sample of patients and use it to make inferences to a larger population. This presentation will consider how registries can be used, some of the pitfalls awaiting the unsuspecting registry researcher; and approaches that will give the best chance of success.
Dirk Ubbink, MD
"The effectiveness and costs of hyperbaric oxygen therapy for diabetic ischemic ulcers: results of the DAMOCLES multicenter trial"
This trial was conducted in 9 hyperbaric centers and 25 referring hospitals to find out whether additional HBOT would benefit patients with diabetes and ischemic leg ulcers. We randomized 120 diabetic patients with an ischemic wound to standard care without (SC) or with HBOT (SC+HBOT). Primary outcomes were limb salvage and wound healing, amputation-free survival (AFS), and direct and indirect medical costs.
Limb salvage was achieved in 47 patients in the SC group vs. 53 patients in the SC+HBOT group. After 12 months, 28 index wounds were healed in the SC group vs. 30 in the SC+HBOT group. AFS was achieved in 41 patients in the SC group and 49 patients in the SC+HBOT group. In the SC+HBOT group 21 patients (35%) were unable to complete the HBOT-protocol as planned. Those who did had significantly fewer major amputations and higher AFS. Overall costs were slightly higher in the SC+HBOT-group.
Michael Strauss, MD
"The Long Beach Wound Score as a Validated Tool for Comparative Effectiveness Research of Wounds and Objectifying the Indications for Hyperbaric Oxygen"
The Long Beach Wound Score (LBWS) is a validated wound scoring system that is user-friendly, intuitively obvious and applicable for all wounds - not just diabetic foot ulcers. Five assessments, each graded from 2-points (best possible) to 0-points using objective criteria to grade each, are summated to generate 0 to 10-point scores.
The scores then quantify three wound categories; "Healthy" 7.5 to 10 points, "Problem" 3.5 to 7 points and "End-stage" 0 to 3 points. The assessments include 1) Appearance of the wound base, 2) Size--including undermining, 3) Depth--to wound base or bottom of a tract, 4) Infection and 5) Perfusion.
For wounds in the "Healthy" category only simple wound care and, occasionally, biologics are needed for management. Deep infection, deformity, and/or ischemia are invariable present in the "Problem" wound category. These require debridements and antibiotics plus revascularization and/or hyperbaric oxygen (HBO2). Juxta-wound transcutaneous oxygen measurements in room air and with HBO2 objectify when this modality is indicated for wound management. Wounds in the "End-stage" category require amputation or revascularization if salvage is indicated. The decision for amputation versus salvage in a "Transition" zone (LBWS in the 2.5 to 4 point range) require information about the patients' wellness and goals, both quantified by 0 to 10 scores as intuitively obvious and easy to use as the LBWS.
With 24 billion dollars a year being spent in the USA for management of chronic wounds, comparative effectiveness research (CER) is needed to evaluate the effectiveness, cost benefits, and convenience of wound care. The essential consideration for CER is using a wound scoring system that objectifies the evaluation so "like can be compared with like." The LBWS is the reliable (similar scores by two or more observers) and validated tool that meets this requirement. With the LBWS the UHMS has the potential to establish a registry, document the effectiveness of interventions and become the "go to" source for payers to justify authorizations for wound management including HBO2 treatments.
Saturday, June 30
Enrico Camporesi, MD
"Hyperbaric Oxygen Therapy for Aseptic Necrosis of the Femoral Head andof the Femoral Condyli"
Osteonecrosis of the knee (ONK) is a form of aseptic necrosis resulting from ischemia to subchondral bone tissue. Typically, common surgical treatments are invasive and palliative or time-limited. Hyperbaric oxygen (HBO2) therapy may provide a non-invasive alternative by improving oxygenation and reperfusion of ischemic areas, both for distal femoral condyli, as recently described, or for a similar malady of the femoral head, previously published.
We recently described 37 ONK patients (29 male, 8 female; mean age ±1 SD: 54±14). 83.7% of patients presented with Aglietti stage I-II; 16.3% presented with Aglietti Stage III. Patients were treated with HBO2 once a day, five days a week, at 2.5 ATA with 100% inspired oxygen by mask for an average of 67.9±15 sessions. Magnetic resonance imaging was performed before HBO2, within one year after completion of HBO2, and in 14 patients, 7 years after treatment. Oxford Knee Scores (OKS), an index of functionality, where 60 is normal, were recorded before HBO2 and at the end of each HBO2 treatment cycle.
After the 30 sessions of HBO2, 86% of patients experienced improvement in their OKS, 11% worsened, and 3% did not change. All patients improved in OKS after 50 sessions. MRI evaluation 1 year after HBO2 completion showed that edema at the femoral condyle had resolved in all but one patient. MRI at 7 year after completing therapy were all normal. In conclusion, HBO2 is beneficial in ONK. Patients experienced improvements in pain and mobility as demonstrated by improvement in OKS. Radiographic improvements were also seen upon post treatment follow-up. Aglietti staging for the entire sample saw an aggregate decrease (p < 0.01) from 1.7 ± 0.7 to 0.3 ± 0.6.
Gerardo Bosco, MD
Pre-conditioning (PC) has been described as the hyperbaric oxygen (HBO2) experience before a critical event, with the aim to prevent a specific clinical condition, and its development as a valuable complement both in diving medicine (Bosco, 2010) as well as prior to ischemic or inflammatory situations. PC is a preventive treatment that triggers endogenous cascades, which can protect from stress-activated and stress-reactive responses. A possible mechanism of HBO-PC mediating beneficial effects has been described as attenuation of the production of proinflammatory cytokines in response to an inflammatory stimulus such as surgery and modulation of the immune response. HBO-PC protocols are performed at 2.0–2.5 atmospheres absolute (ATA), and usually only applied for one or a few days. The physical adaptations in response to alterations in atmospheric oxygen appear to extend not only to survival, but also a preconditioned state.
Similar to ischemic and stress preconditioning, many different paradigms have been used to demonstrate that either rapid or delayed tolerance is affected by the HBO2 therapy. Irrespective of the cause of injury, inflammatory cytokines released after the primary event trigger leukocyte activation and free radical release, causing secondary damage and extension of injury. Thus, modulating inflammatory molecules has the potential benefit of limiting leukocyte-mediated extension of injury. Many studies demonstrated a protective mechanism of HBO-PC in the injured brain, heart, or liver. Previous data by Yang and colleagues on animals demonstrated that HBO2 inhibits TNF-α production during intestinal, brain and muscle ischemia-reperfusion and it has a beneficial effect, mediated by decreased production of IL-6, IL-1β, dopamine and lactate (Bosco, 2007; Yang, 2001;2006;2010). Studies on animals showed that HBO-PC can protect the brain from ischemia-reperfusion injury and that Sirt1 is a potential molecular target for therapeutic approaches (Ding, 2017). In man, HBO-PC induces endogenous cardioprotection subsequent to ischemic reperfusion injury (Allen, 2014).
Additionally, clinical HBO-PC showed effects before surgery. A single preoperative hyperbaric oxygen treatment on the day before surgery may reduce the complication rate in pancreatic resection (Bosco, 2014). In liver surgery, studies demonstrated to increase the number of new cells and the density of microcirculation in the regenerating liver after HBO-PC (Theodoraki, 2011). Furthermore, hyperbaric oxygen preconditioning improves postoperative dysfunctions by reducing oxidant stress and inflammation (Gao, 2017). A recent experimental paper has identified an important mechanism involved in triggering the beneficial effect of HBO-PC, as the intracellular induction of heme-oxygenase-1 in hepatic IR injury. Moreover, in dive medicine HBO-PC reduced bubble formation and platelets activation; HBO-PC might enhance lymphocyte antioxidant activity and reduce reactive oxygen species levels. Pre-breathing oxygen in water may also preserve calcium homeostasis, suggesting a protective role in the physiological lymphocyte cell functions (Bosco, 2010; Morabito, 2011).
Whether the various preconditioning protocols contribute to the different results should be investigated in further studies and applied to diverse surgical procedures, especially major surgeries leading to postoperative ICU admission. Therefore, HBO-PC is an encouraging and feasible therapeutic strategy for protecting organs from the subsequent lethal stimulus.
- Ding P, Ren D, He S, He M, et al (2017). Sirt1 mediates improvement in cognitive defects induced by focal cerebral ischemia following hyperbaric oxygen preconditioning in rats. Physiological research, 66(6).
- Yang ZJ, Bosco G, Montante A, Ou XL and Camporesi EM (2001) Hyperbaric O2 reduces intestinal ischemia-reperfusion-induced TNF-a production and lung neutrophil sequestration. Eur J Appl Physiol 85: 96-103
- Yang Z, Nandi J, Wang G, Bosco G, et al. (2006) Hyperbaric Oxygenation ameliorates indomethacin-induced enteropaty in rats by modulating TNF-a and IL-1 b production. Dig Dis Sci 34(1-2):70-6.
- Bosco G, Zj Yang, J Nandi, Jp Wang, et al. (2007) Effects of hyperbaric oxygen on glucose, lactate, glycerol and antioxidant enzymes in the skeletal muscle of rats during ischemia and reperfusion. Clin Exp Pharmacol Physiol 34, 70-76.
- Yang Zj, Bosco G, Xie Y, Chen Y, Camporesi EM. (2010) Hyperbaric oxygenation alleviates MCAO-induced brain injury and reduces hydroxyl radical formation and glutamate release. Eur J Appl Physiol. Feb;108(3):513-22.
- Bosco G, Yang Zj, Di Tano G, Camporesi EM, et al. (2010) Effect of in-water versus normobaric oxygen pre-breathing on decompression-induced bubble formation and platelet activation. J Appl Physiol. May;108(5):1077-83.
- Morabito C, Bosco G, Pilla R, Corona C, et al. (2011) Effect of pre-breathing oxygen at different depth on oxydative status and calcium concentration in lymphocytes of scuba divers. Acta Physiol (Oxf). May;202(1):69-78.
- Bosco G, Casarotto A, Nasole E, Camporesi E, et al. (2014). Preconditioning with hyperbaric oxygen in pancreaticoduodenectomy: a randomized double-blind pilot study. Anticancer research, 34(6), 2899-2906.
- Theodoraki K, Tympa A, Karmaniolou I, Tsaroucha A, et al. (2011). Ischemia/reperfusion injury in liver resection: a review of preconditioning methods. Surgery Today, 41(5), 620.
- Gao Z. X, Rao J, & Li Y. H. (2017). Hyperbaric oxygen preconditioning improves postoperative cognitive dysfunction by reducing oxidant stress and inflammation. Neural regeneration research, 12(2), 329.
- Allen M, Golembe E, Gorenstein S, Butler G. Protective effects of hyperbaric oxygen therapy (HBO2) in cardiac care-A proposal to conduct a study into the effects of hyperbaric pre-conditioning in elective coronary artery bypass graft surgery (CABG) Undersea Hyperb Med. 2014;42:107–114.
Shai Efrati, MD
- Basics pathophysiological cascade of non-recoverable brain injuries.
- The neuroplasticity effect of hyperbaric oxygen therapy
- Selecting the optimal candidate for the treatment
Clinical studies published in recent years present convincing evidences that hyperbaric oxygen (HBO2) therapy can be the coveted neurotherapeutic method for brain repair of neurological incidents like traumatic brain injury and stroke. This new understanding leads to a paradigm change in the way that we refer to chronic brain injuries; from now these should be thought of like other non-healing wounds in other parts of the body.
The classical candidate for HBO2 is a patient with unrecovered brain injury where tissue hypoxia is the limiting factor for the regeneration process. In this patient, HBO2 may induce neuroplasticity in the stunned regions where there is a brain anatomy/physiology mismatch (as for example PET/MRI).
In this lecture we will discuss the multifaceted role HBO2 can play in neurotherapeutics based on recent persuasive evidence demonstrating HBO2 efficacy in brain repair as well as a new understanding of brain energy management and response to brain damage. We will also discuss how to select suitable candidates and how to choose the optimal HBO2 protocol for the selected candidate.
Brian Keuski, MD; Fellow, Duke Hyperbarics
"Diving medicine literature update"
Take a whirlwind tour through the last 12 months of diving medicine literature. Major topics include: decompression illness, fitness to dive issues, immersion pulmonary edema, and diving physiology.
Lince Varughese, MD; Fellow, LSU Hyperbarics
"Hyperbaric medicine literature update"
Dr. Varughese will give a brief update on key articles in recent hyperbaric medicine literature; novel ideas and newfound wisdom.
Gerardo Bosco, MD
"Adaptive mechanisms in breath-hold divers"
The human body faces extreme physiological challenges while immersed with voluntary breath-holding. Breath-hold diving is potentially associated to extreme environmental factors such as increased hydrostatic pressure, hypoxia, hypercapnia, hypothermia and strenuous exercise. Physiological adaptations can depend among the time of breath suspension and the depth of diving. While descending chest squeeze and blood redistribution occur. Indeed, blood as being an incompressible fluid from peripheral circulation is shifted to the chest. The intrathoracic blood volume increases. Moreover, face immersion results in induced bradycardia, due to the diving reflex. Conversely, breath-holding at rest, out of water, induces non-significant changes in heart rate. Breath-hold swimming, even on the surface, instead causes pronounced bradycardia. During deep diving a higher O2 consumption and a fall in alveolar and blood O2 content was observed. Consequently, alveolar CO2 pressure increases due to chest compression while descending.
It was supposed that the maximum reachable depth in breath-hold diving was determined by the relationship between total lung capacity and residual volume. Craig suggested a compensatory physiologic mechanism to explain why thoracic implosion does not occur and hypothesized that a certain amount of blood was diverted from the peripheral circulation into the chest. Intrathoracic pressure in such a condition represented the elastic behavior of the chest wall when exposed to high hydrostatic pressure. The increased hydrostatic pressure at depth reduces pulmonary gas volumes and consequently increases intrathoracic blood volume, with enlargement of the right heart chambers and pressures. On the contrary, the left sections of the heart do not undergo any enlargement, and do not show any sign of pressure increase. The systolic stroke volume is the consequence of Starling’s law: the blood shift stretches the heart and increases the intracardiac volume. This certainly means that, although rarely exploited in nature, anaerobic metabolic reserve represents a resource for survival of the animal. The same can be said for high-altitude hypoxic environments.
Another consideration is the “graded response” to breath-hold diving in relation to the level of physiological stress and to the control by the central nervous system. The diving response is a strategic adaptation to hostile environmental conditions common to many animals but human breath-hold divers require knowledge for the safe and health of participants.
Peter Lindholm, MD
"Pulmonary pathophysiology in deep breath-hold diving"
Deep breath-hold diving may expose the lungs to the limits of known human physiology. We will discuss barotrauma of descent with pulmonary edema, glossopharyngeal hyperinsufflation and arterial gas embolism.
Alessandro Marroni, MD
"Breaking news on breath-hold diving research"
Recent data from field research on pathophysiology of breath-hold diving will be presented, with a particular focus on breath-hold diving-induced pulmonary edema, Taravana, epidemiology, mechanisms, pathogenetic hypotheses and data on genetic predisposing factors.