#hbot

BY BROOKS LEITNER

Imagine lying back in an enclosed chamber where you bask for 90 minutes in a sea of pure oxygen at pressures two to three times that felt at sea level. This is the world of hyperbaric oxygen therapy (HBOT), a technology that’s been around for decades and is now being explored as a possible treatment for Long COVID.

"The silence on the inside is deafening at first,” says John M.,* who has undergone dozens of HBOT treatments for his persistent Long COVID symptoms. Fortunately, there is a television outside the chamber in view, and it is easy to communicate with the provider if needed. While the potential protocol is still being refined, patients may undergo up to 40 HBOT sessions to address some of the most problematic, lingering symptoms of this complex condition.

HBOT is a therapeutic process that has been widely used to treat such conditions as decompression sickness in scuba divers, carbon monoxide poisoning, and diabetic foot ulcers. In HBOT, the body is exposed to 100% oxygen, a significant increase from the 21% oxygen concentration we typically breathe. The therapy takes place in an enclosed chamber where the air pressure is elevated above normal levels. The combination of high-pressure and high-oxygen conditions enhances the amount of oxygen that can reach the body's tissues. The hope is that this therapy can provide the same relief and healing to people with Long COVID that it does for those with other conditions.

According to John M., HBOT was the first treatment that helped with his sleep and reduced his heart palpitations. “At one point after hospitalization, my Long COVID symptoms were so bad that I could barely walk or talk. HBOT was a great tool that really assisted with my recovery,” he said. John added that he hopes the medical community will achieve a better understanding of how HBOT can help relieve suffering for patients with Long COVID and that more research will increase access to this innovative therapy.

Does HBOT improve Long COVID symptoms? One key observation from the work of Inderjit Singh, MBChB, an assistant professor at Yale School of Medicine (YSM) specializing in pulmonary, critical care, and sleep medicine, is that Long COVID patients often experience debilitating fatigue. Based on Dr. Singh’s previous Long COVID research, the exhaustion is thought to be linked to the muscles’ inability to efficiently extract and utilize oxygen.

To picture how HBOT might work, you can think of your muscles as engines sputtering, struggling to get the fuel they need. If oxygen is the gas that fuels the muscles, it’s as if you are trying to complete your daily routine while the gas tank is running on “empty.” By aiming to directly address this oxygen utilization impairment, HBOT may be a potential solution.

A systematic review by researchers at the China Medical University Hospital noted that HBOT could tackle another major factor in the Long COVID puzzle: oxidative stress. This relates to the body's struggle to maintain balance when harmful molecules, known as free radicals, run amok, causing chronic inflammation.

Research co-authored by Sandra K. Wainwright, MD, medical director of the Center for Hyperbaric Medicine and Wound Healing at Greenwich Hospital in Connecticut, suggests that HBOT, with its high-oxygen environment, might dampen this chronic inflammation by improving mitochondrial activity and decreasing production of harmful molecules. Other potential benefits of HBOT in the treatment of Long COVID may include restoration of oxygen to oxygen-starved tissues, reduced production of inflammatory cytokines, and increased mobilization of hematopoietic stem cells—primary cells that transform into red blood cells, white blood cells, and platelets.

HBOT for Long COVID: Current and ongoing research Several small-scale reports have indicated that HBOT is safe for patients with Long COVID.

To address this question, a trial that followed the gold standard of modern medical research—a randomized, placebo-controlled, double-blind design—assigned 73 Long COVID patients to either receive 40 sessions of HBOT or a placebo of only 21% oxygen. The study observed positive changes in attention, sleep quality, pain symptoms, and energy levels among participants receiving HBOT. In a longitudinal follow-up study published in Scientific Reports, the authors at the Tel Aviv University found that clinical improvements persisted even one year after the last HBOT session was concluded. In a second study, the same authors focused on heart function, measured by an echocardiogram, and found a significant reduction in heart strain, known as global longitudinal strain, in patients who received HBOT.

In another study, 10 patients with Long COVID underwent 10 HBOT treatments over 12 consecutive days. Testing showed statistically significant improvement in fatigue and cognitive function. Meanwhile, an ongoing trial at the Karolinska Institute in Sweden has reported interim safety results wherein almost half of the Long COVID patients in the trial reported cough or chest discomfort during treatment. However, it was unclear whether HBOT exacerbated this symptom or if this adverse effect was due to the effort of participation by patients suffering from more severe Long COVID symptoms.

Is HBOT currently available as a treatment for Long COVID? For HBOT to become a mainstream treatment option for Long COVID, several critical priorities must be addressed. First, there is currently no established method for tailoring HBOT dosages to individual patients, so researchers must learn more about the specific features or symptoms that indicate potential benefits from HBOT. At the same time, we need to identify factors that may be associated with any adverse outcomes of HBOT. And finally, it’s important to determine how long these potentially beneficial effects last in a larger cohort. Will just a few HBOT trials be enough to restore patients to their baseline health, or will HBOT become a recurring component of their annual treatment regimen?

For now, HBOT remains an experimental therapy—and as such is not covered by insurance. This is a huge issue for patients because the therapy is expensive. According to Dr. Wainwright, a six-week course of therapy can run around $60,000. That’s a lot to pay for a therapy that’s still being studied. In the current completed studies, different treatment frequencies and intensities have been used, but it’s unclear how the treatment conditions affect the patient’s outcome.

“I have had some patients notice improvements after only 10 or 15 treatments, whereas some others need up to 45 treatments before they notice a difference,” notes Dr. Wainwright. “I think that HBOT is offering some promising results in many patients, but it is probably a strong adjunctive treatment to the other spectrum of things Long COVID patients should be doing, like participating in an exercise, rehab, and nutritional program.”

Dr. Singh notes that “a major challenge for research is the heterogeneity of Long COVID. It is hard to determine which symptoms to treat and enroll patients into trials based on them.”

Perhaps treatments that target multiple issues caused by Long COVID, like HBOT, may help overcome this challenge.

*Not his real name.

Brooks Leitner is an MD/PhD candidate at Yale School of Medicine.

The last word from Lisa Sanders, MD: Hyperbaric oxygen therapy (HBOT) is just one of the many existing treatments that are being looked at to treat Long COVID. We see this with many new diseases—trying to use a treatment that is effective in one set of diseases to treat another. And there is reason for optimism: We know that HBOT can deliver high levels of oxygen to tissues in need of oxygen. That’s why it’s used to treat soft tissue wounds. If reduced oxygen uptake is the cause of the devastating fatigue caused by Long COVID, as is suggested by many studies, then perhaps a better delivery system will help at least some patients.

Studies referenced:

bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-023-08002-8

www.ncbi.nlm.nih.gov/pmc/articles/PMC8806311/

www.nature.com/articles/s41598-024-53091-3

www.nature.com/articles/s41598-022-15565-0

www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1354088/full

The Basics

Wait - what? HOW? Try not to have PTSD from your days in chemistry, but remember these?

The treatment physiology of hyperbarics relies on gas laws. Recall that it takes a lot of pressure to dissolve a gas into a liquid.

We use pressure to force oxygen into the blood stream at high rates to facilitate wound healing. For reference, most of your oxygen content is bound to hemoglobin (~98%). You do have dissolved oxygen in your blood, represented by your PaO2/PvO2 in a blood gas. However, this makes up a fraction of O2 content (~2%: if you want a clinical soap box, you should hear me talk about blood gases to students lol). A normal ABG would have a PaO2 of 65-100. An ABG acquired during hyperbaric treatment would be well over 2,000.

As an aside, recall that ambient air is 21% oxygen. Also, as a reminder, we exist at 1.0 ATA of pressure (one atmosphere).

How is it done?

Delivering oxygen this way requires delivery of a lot of pressure. We utilize dive chambers for this purpose. There are two types of chambers:

Monoplace: literally looks like a class coffin. Holds one patient and delivers oxygen at pressure through the entire chamber. These are very popular at wound centers.

Multiplace: literally looks like a submarine. Holds 2+ patients and delivers oxygen at pressure to individual patients hooked up to hoods or masks. These are found at tertiary care/academic medical centers.

Literally, the multiplace hoods make you look like a silly space person.

The reason oxygen is delivered this way in a multiplace chamber is to reduce the risk of fire. Oxygen at pressure can go boom. Having an entire chamber full of O2 is a big risk. So, we deliver the gas individually to each patient.

How did it start?

Dinking around with gases at pressure has been a thing for 400 years. However, it didn't become a more focused endeavor until the first dive suits started to be a thing in the 1870s. The specialty itself is relatively new, developed in the 1930s due to advent of decompression illness with divers. Things really progressed in the 1950s.

One pivotal study was "Life without Blood" in 1959. Dr. Boerema proved that he could keep a pig alive with HBO alone. The ethics of this experiment are questionable but he exsanguinated a pig under hyperbaric conditions (3.0 ATA, 100% FiO2). Plasma was left behind. By doing this, he proved that, at pressure, an organism does not need hemoglobin to live. Kind of a radical thing to prove! Don't worry, the pigs did get their blood back and recovered without issue.

What is treated with HBOT? (hyperbaric oxygen therapy)

Anything related to wound healing can be treated with HBOT. We also treat carbon monoxide poisoning, air gas embolism, and decompression sickness with HBOT. I'll start with those since they are (imo), the most clinically interesting. ;-D

Carbon monoxide poisoning: The physiology of using HBOT to treat CO poisoning is based on the binding affinity of CO to hemoglobin. CO has 200 x the binding affinity for hemoglobin than O2 or CO2 does. Because the binding sites are taken up by CO, hemoglobin cannot pick up O2. It also can't offload whatever O2 is already bound. The goal with HBOT is to bombard the blood with massive amounts of O2 to force CO off.

For reference, it would take about 6 hours for CO to offload on its own from hemoglobin on room air. It would take half as long at 100% FiO2 delivered at standard air pressure (1.0 ATA). CO is rapidly forced off within 30 minutes with HBOT. With very severe CO poisoning, particularly in cases of LOC, this is vital for limitation of hypoxia and neurological sequelae of exposure. Treatment is 1-3 "dives" depending on clinical context. The patient is treated at 2.8 ATA (60 feet of sea water) for about 120 minutes.

Air gas embolism: This occurs when gas is accidentally introduced into circulation. It can either be venous or arterial. The venous system has much more flexibility in tolerance for air bubbles. 15 cc or less of gas introduction is probably not going to result in symptoms. Higher volumes go to the lungs and can result in local lung infarction.

The real danger with this is air introduced into arterial circulation. Depending on where it is introduced, it can go directly to the heart causing an MI, or to the brain causing a stroke. Any volume of air introduced into arterial circulation is bad news bears. Treatment is usually 1 "dive" but could be more based on the context. The patient is treated at 2.8 ATA for 30 minutes and then the ascent is extremely slow. The whole dive takes about 5 hours. Why so long? If we ascend too quickly, the air bubble will reform.

Decompression sickness: This occurs primary with scuba divers who ascended too quickly. Scuba divers generally breath mixed gas, most commonly air (21% O2, ~79% N2) or nitrox (35% O2, ~65% N2). As someone is diving, the nitrogen they breath is also dissolved into their blood since they are at a pressure greater than 1.0 ATA. If a diver ascends too quickly, the nitrogen dissolved in the blood will rapidly reform air bubbles in the blood. We just mentioned how that is problematic.

Since air bubbles can go everywhere in circulation, the symptoms are variable ranging from headache, vertigo, nausea, joint pain, chest pain, stroke symptoms, loss of bowel/bladder function, etc. The treatment for this is to recompress the patient and very slowly ascend in the HBO chamber. Treatment is usually 1 dive but could be more based on the context. The patient is treated at 2.8 ATA for 30 minutes and then the ascent is extremely slow. The whole dive takes about 5 hours. Why so long? Again, if we ascend too quickly, the air bubble will reform.

Wound related conditions: there are roughly 15 approved diagnoses for HBO by Medicare in the USA. This is important to mention because if a condition is not covered, paying out of pocket is extremely cost-prohibitive. Insurance is billed $6,000 per treatment! Some of the most common conditions treated are osteoradionecrosis, soft-tissue radionecrosis, irradiation cystitis with hematuria, and refractory chronic osteomyelitis. Wounds created from radiation exposure have the best evidence to support the use of HBOT. These are considered outpatient conditions so patients come to be treated Monday-Friday. We dive to 2.4 ATA for 120 minutes. At minimum, patients are prescribed 20 dives but most treatment protocols for radiation induced injuries is at least 40 dives.

As you can see, this is a HUGE commitment for the patient. One dive is not enough for these wound related conditions. As a hyperbaric provider, I can say that we have patients with such significant symptom relief from HBO. For example, irradiation cystitis with hematuria is extremely debilitating. Patients are fatigued from chronic blood loss, deal with painful bladder spams and pelvic pain, pain with urination, and increased frequency. The blood can clot and obstruct their urethra or foley catheter. Symptoms like this limit quality of life. HBOT makes a huge difference for them.

Benefits

Anyone who has barriers to wound healing can benefit from HBO. Barriers include vascular disease, CKD, COPD, DM, heart failure, and immunocompromised status. The goal is symptom resolution/improvement or healing of the wound. Some patients get approved for far more treatments than we typically do. Usually the maximum insurance will cover is 60. However, in some situations, the clinical benefit of continued treatments is recognized by insurance and treatment is extended.

As a provider, I get to know these patients pretty well. They show up every day that I am staffing in HBO and it is rewarding to see them improve. Compared to my critical care role, this is a nice change of pace.

Adverse Reactions and Risks

There are risks and side effects to HBO. The most common are barotrauma, pneumothorax, seizure, temporary worsening of cataracts/vision, and abdominal distention.

Barotrauma of the ears and sinuses is by the most common issue we face in HBOT. If patients are not able to clear their ears as they descend ("pop" their ears), they can rupture their ear drums. Patients that cannot descend without extreme pain may need myringotomy tubes (ear tubes) to assist with equalizing pressure.

Seizure is a risk of HBOT and that primarily comes from oxygen reducing the seizure threshold. We mitigate this with "air breaks". These are 5 minutes intervals of the treatment where the patient is receiving air rather than 100% O2. Example, we treat at 100% for 30 minutes, have a 5 minute air break, repeat x 2. Obviously the people at highest risk are those with epilepsy or taking seizure threshold reducing medications.

HBOT can worsen cataracts and vision temporarily. The mechanism of this is poorly understood but we know it is reversible. Distance vision is affected the most.

Contraindications

The only absolute contraindication to HBOT is an untreated pneumothorax. There are many relative contraindications that require a risk benefit analysis. An example of this is pregnancy. HBOT has not been thoroughly studied in pregnancy and is not recommended EXCEPT in cases of CO poisoning where we know that the CO concentration is higher in fetal circulation than maternal. Always treat a pregnant person with CO poisoning.

Other potential contraindications include use of certain chemotherapy agents, COPD with blebs/bullae, severe heart failure, epilepsy, sinus/HEENT disease, claustrophobia, certain implanted devices, or active infection.

With certain chemo agents, they can lower the seizure threshold putting patients at higher risk of seizure in the chamber. People with COPD and blebs are at risk of those blebs popping under pressure and causing acute respiratory distress. People with heart failure can experience flash pulmonary edema after an HBO treatment. If people are claustrophobic, obviously spending time in a monoplace chamber can trigger panic attacks. At my center, we sometimes have people referred to our multiplace chamber for exactly that reason.

Most implanted medical devices are HBOT compliant. Generally, pacers and other devices are tested at 4.0 ATA of pressure. We double check with the manufacturer that the device is compliant. If it isn't, we cannot safely treat and have to deny the consult.

Obviously, if someone is sick, we don't want them in the chamber. Particularly colds, severe allergies, fever, or anything that is affecting HEENT. People with acute sinus infection are unable to clear sufficiently to dive. Even if they can clear, they feel miserable. No need to go through that.

Safety Issues

I mentioned that high O2 environments are at risk for explosion. Safety is the number one concern with any chamber. The goal is to reduce risk of fire by removing fabrics that create static (anything synthetic), removing electronic devices that are not HBOT approved, and going through multiple levels of safety checks for patients and for chamber preparation.

At our chamber, only 100% cotton is allowed in the chamber. All patients have special scrubs that they wear during treatment. No electronic devices can be brought in the chamber which includes phones, tablets, laptops, e-readers, watches, pagers, etc. We do have HBOT approved IV pumps and radio headsets that we use. These have been tested at 4.0 ATA. The radio headsets are for the attendant (staff member) who is in the chamber and this is also for safety purposes. Since we have a mulitplace chamber, a staff member is always in the chamber with the patient(s).

One thing I do want to address is that some people are concerned about putting a patient with active cancer into the chamber. There is concern that the high O2 environment will "feed" the cancer. There is simply not data to support this. Active cancer is not a contraindication to HBOT.

And there you have it! The down and dirty of HBOT! Hopefully you learned something cool. If you think you have a patient who would benefit, find your local HBOT provider. We are always happy to talk with you about the process. If you care about a soapbox of how insurance companies suck, see below. :-D

Soapbox: I will say, I have definitely been frustrated with insurance companies. They are the gatekeepers of this treatment. You can have several providers supporting the use of treatment and an insurance company can still say "no". Very frustrating.

A prime example of this are patients who have avascular necrosis that is steroid or chemotherapy induced. These are often younger patients (late teens, early 20s) who have/had leukemia of some kind. They end up having necrosis at a joint, usually the femoral head, that will likely result in complete joint replacement at a young age. No orthopedic surgeon wants to replace joints on a young person. It comes will all kind of problems and always needs revision later in life.

Insurance companies will say "we only cover radiation induced necrosis" because that is what the literature supports. Yes, they are correct that the vast majority of studies support HBOT for radiation induced injury. However, the pathophysiology of the tissue destruction, while a little different, ends up with the SAME problem. There are studies that support HBOT use in these situation but not nearly as many as radiation induced injury. The result is that patients suffer, get a joint replacement they could have avoided (or postponed until they are fully developed), and generally are shafted.