Medical/Patient Care

If a patient with a Wagner Grade 3 ulcer has osteomyelitis that has failed all conservative measurement is being worked up for HBO. He continues to work as a EMT and does 24 hour shifts twice a week, including weekdays and can only commit to HBO three days a week. Would this be acceptable therapy for the chronic osteomyelitis, or would this be considered inappropriate if the therapy is not done five days a week. I don't want the commercial insurance company coming back and requesting their payment bac

Postd: 12/7/2020

Q:
A patient with a Wagner Grade 3 ulcer has osteomyelitis that has failed all conservative measurement is being worked up for HBO. He continues to work as a EMT and does 24 hour shifts twice a week, including weekdays and can only commit to HBO three days a week. Would this be acceptable therapy for the chronic osteomyelitis, or would this be considered inappropriate if the therapy is not done five days a week. I don't want the commercial insurance company coming back and requesting their payment back.

A:
The standard treatment with HBO2 is 5 treatments per week for chronic osteo or for Wagner’s 3 diabetic foot ulcers. We don’t know whether a course of treatment with substantially fewer than 5 treatments per week will be effective. This has never been studied. Another issue of course is while he is working as an EMT he is likely on his feet for a good portion of the time making offloading very difficult. We can’t predict what the insurance company will do. You might think of a course of HBO2 on a 3 times a week basis or some other less than 5 treatment per week course as being analogous to taking an antibiotic only for a few days each week. It is very unlikely to be successful. I would try to prevail upon the patient to take a leave of absence (hopefully with some kind of pay) to address his problem with a multi-disciplinary treatment including aggressive antibiotics, HBO2, appropriate surgical debridement and adequate offloading.

John J. Feldmeier, D.O.

Is there any salutary effects for the use of HBO in aggressive glioblastoma ?

As yet, there are no approved or reimbursed indications for HBO2 and the treatment of GBM or the complications of its treatment except for the treatment of radiation necrosis. Please see the attached. It comes from a draft of the about to be published update of the Indications BOOK (HBO2 Committee Report). As such it is unpublished data,.and as such its reproduction is prohibited.

John Feldmeier

61 year old patient with bilateral optic neuropathy secondary to radiation. Has recently been started on prednisone 80mg daily, vitamin E 1000U daily, and pentoxifylline 400mg TID by neuro-ophthalmology. I know the steroids can increase oxygen toxicity, but that the Vitamin E also decreases this risk. Not sure if they offset each other. No seizure history, no pulmonary history, no history of tobacco use. Plan would be 90 minutes at 2.0 ATA with one 5 minute air break? Should number of air breaks be

Other history: Previously healthy male diagnosed with grade 4 glioblastoma 10/2017 s/p resection and chemoradiation (completed 1/2018).  Loss of visual acuity bilaterally x 4 weeks, with nearly complete loss of vision on the right.  MRI consistent with radiation optic neuropathy.  Patient hoping to preserve what vision he has left.  Understands data is limited.  Also noteworthy, patient has a known atrial septum defect with bidirectional shunting.

A: Treatment for this disorder is recommended. I am always in favor of 2.4 ATA for treatment of radiation injuries especially of the CNS. Many if not most of these patients  are on steroids. In the fairly large series from Laurie Gesell while at U of Cincinnati, these folks were not prone to O2 related seizure though certainly this can happen. The known septal defect is not an issue because we are not talking about an air dive. Treatment with Vitamin E might offer some slight protection. If I were to treat this patient, I would treat 3 30 min periods with 5 minute airbreaks at 2.4 ATA and only depart from this if there was a seizure. Informed consent of course is important. This profile chosen because of the severity of the condition and the track record in treating radiation injuries at 2.4 ATA-also the animal study by Marx et al. The profile you suggest is certainly safe but may not be as effective.

John Feldmeier, DO

Anybody have any experience treating pneumocephaly (complication of epidural injection) with HBOT?

Unless there is a clinical problem besides the presence of air (while will resolve on its own), I see no reason to treat. If there is a desire to accelerate resolution, 100% O2 administration at 1 ATA will do that.

The question concerns a 49-year-old otherwise healthy woman who presented in 2017 with complaints of progressive noise magnification and severe headaches.

There are several anecdotal reports of HBO2 for brain necrosis. In some radiosurgery series, the incidence of brain necrosis is as high as 25%.As with all CNS injuries early intervention is likely to have a higher rate of success. Determinants of outcome obviously include neurologic symptom response, but some series report decreases in steroid requirements and improvement on brain imaging mostly MRI. In my reading of the literature Avastin does not give consistent response.

I would recommend at least 40 treatments at 2.4 ATA. Many patients appear to require a good number of treatments for sustainable response, perhaps well over 60.To my knowledge no one has reported a higher likelihood of seizures during HBO with this group. If seizure activity is part of the picture adequate coverage with anti-convulsants is obviously needed.

See the below abstract and some pdf of slides from one of my presentations.

John Feldmeier

• Hyperbaric oxygen treatment for post-radiation central nervous system injury: a retrospective case series.
  Undersea Hyperb Med. 2014 Mar-Apr;41(2):87-96.
  Valadão J, Pearl J, Verma S, Helms A, Whelan H.
  

• CNS-Brain Necrosis
  John Feldmeier, DO

Can you clarify? For dx of DFU 3 or higher, one of the qualifiers for HBO is that patient failed 30 days of wound care. If the patient''s wound was only a DFU 2 during those 30 days, does that count or does the wound need to be a DFU 3 during those 30 days?

CMS clearly states must be Wagner Grade III or higher. See links below for the NCD and also for the UHMS CPG for Diabetic Foot Ulcer.

• National Coverage Determination (NCD) for Hyperbaric Oxygen Therapy (20.29)
• A clinical practice guideline for the use of hyperbaric oxygen therapy in the treatment of diabetic foot ulcersin the treatment of diabetic foot ulcers
  UHM 2015, Vol. 42, No. 3
  CPG Authors: Enoch T. Huang, Jaleh Mansouri, M. Hassan Murad, Warren S. Joseph, Michael B. Strauss, William Tettelbach, Eugene R. Worth
  UHMS CPG Oversight Committee: Enoch T. Huang, John Feldmeier, Ken LeDez, Phi-Nga Jeannie Le, Jaleh Mansouri, Richard Moon, M. Hassan Murad
  CORRESPONDING AUTHOR: Dr. Enoch T. Huang – enoch.huang@mac.com 

Do you have any safety information or contraindications regarding chemo agent Ibrance and concurrent HBOT?

Posted: 12/7/2020

Q:
Do you have any safety information or contraindications regarding chemo agent Ibrance and concurrent HBOT?

A:

Ibrance is a chemotherapeutic drug in the class of drugs called kinase inhibitors. It works to block one or more enzymes that encourage cellular division in the cancer cells. It is used along with an estrogen blocker (typically an aromatase inhibitor) for the treatment of breast cancer.

As for most of the chemotherapeutic drugs there is no published experience of this drug along with HBO2.

Below, I have copied warnings from the manufacturer in regard to a toxicity of the drug that may react unfavorably with HBO2.

Lung problems (pneumonitis). IBRANCE may cause severe inflammation of the lungs during treatment that can lead to death. Tell your doctor right away if you have any new or worsening symptoms, including:

• chest pain
• cough with or without mucus
• trouble breathing or shortness of breath

Your doctor may interrupt or stop treatment with IBRANCE completely if your symptoms are severe.

Since the drug is known to causse pulmonary toxicities in some patients, I recommend that if the patient receives HBO2, on a daily basis they are questioned as to their pulmonary status. I would also recommend that the patient have auscultation of their lungs before and after each treatment.

I do not believe that there is an absolute contraindication to concurrent treatment.

As always the decision to treat is the purview of the treating physician. Our recommendations are given based on the guidance available and we can assume no responsibility for treatinhg an individual patient in whom we do not have the entire history and whom we have not examined.

John J. Feldmeier, D.O.

Question answered by Dr. John Feldmeier, DO

None of the drugs have a published experience discoverable on a pub med search.

Based on mechanisms of action I doubt any of the drugs would have their toxicities enhanced by HBO2. However, as you know, the decision to treat a patient with HBO2 who is receiving these drugs is the managing physicians decision and our input is meant only to provide guidance based on the information that is discoverable

Response to potential Interaction of HBO and the following chemotherapeutic agents:

1.Faslodex (Fulvestrant): This drug is indicated for ER receptor positive breast cancer most often in combination with other agents. It downregulates the expression of the ER receptor and in doing so interferes with tumor growth stimulated by the ER receptor.

It is given as an IM injection monthly.

Its toxicities include asthenia, mild nausea and vomiting, hot flashes, headaches, injection site reactions back pain and arthralgias and a flu like syndrome.

No published experience with its combination with HBO2, but mechanism of action does not appear to be dependent on O2 presence and I doubt any negative interaction of HBO2 with this drug.

2. 2. Ixempra (Ixabepilone): This drug is a cell cycle specific agent active during the M-phase of cell division. It inhibits the dynamics of microtubules. It is given IV. Its toxicities include myelosuppression,skin rash, hypotension, flushing, fatigue and asthenia, nausea and vomiting and diarrhea, myalgias, arthralgias and other musculoskeletal pain.

Its mechanism of interaction does not appear to be oxygen dependent. No published experience of interaction with HBO2 was found on literature search.

I doubt that there would be any negative interactions with this drug.

3. 3. Ibrance (Palbociclib): This drug is a kinase inhibitor. It interfers with enzymes that promote the activity of certain proteins especially by blocking phosphorylation.

I will append an information sheet on the drug.

No published experience is discoverable with a literature search. Its mode of action does not appea to depend on O2 availabiliity.

I doubt there would be enhanced toxicity with HBO2.

John Feldmeier

Palbociclib

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Palbociclib (codenamed PD-0332991, trade name Ibrance) is a drug for the treatment of ER-positive and HER2-negative breast cancer developed by Pfizer. It is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6.^[1][2]

Contents

 [hide] 

• 1 Mechanism of action
• 2 Approvals and indications
  • 2.1 ER+ breast cancer
• 3 Clinical trials
  • 3.1 HR+ breast cancer
• 4 Pricing
• 5 References

Mechanism of action[edit]

Further information: CDK inhibitor

It is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6.^[1][2]

Approvals and indications[edit]

ER+ breast cancer[edit]

The drug was reviewed and approved under the Food and Drug Administration’s (FDA) accelerated Priority Review and Breakthrough Therapy designation programs on February 3, 2015 as a treatment (in combination with letrozole) for patients with estrogen receptor positive advanced breast cancer.^[3] This was an accelerated approval.^[4]

In March 2017, the FDA granted regular approval to palbociclib for HER2 negative breast cancer, alongsite an aromatase inhibitor. ^[5]

A phase 3 trial, PALOMA-2, was fully enrolled by February 2015 and reported positive results in April 2016.^[6] The results of PALOMA-2 trial (published November 2016) showed significantly longer progression-free survival in patients on palbociclib in combination with letrozole, compared to patients on letrozole and placebo. Progression-free survival was assessed by radiologically confirmed disease progression by RECIST criteria or death during the study. At the time of publication, there was insufficient data on overall survival, and a final analysis is planned after a total of 390 deaths occur per protocol and in agreement with regulatory agencies. Of note, it was noted that the addition of palbociclib caused higher rates of myelotoxic events in the study.^[7]

The drug was approved for use in the European Union in November 2016 as a treatment for hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative locally advanced or metastatic breast cancer either in combination with an aromatase inhibitor or, for women who have received prior endocrine therapy, in combination with fulvestrant. In pre- or perimenopausal women, a luteinizing hormone releasing hormone agonist should also be given.^[8]

Clinical trials[edit]

HR+ breast cancer[edit]

The PALOMA-3 trial announced in April 2015 that the addition of palbociclib was superior to fulvestrant alone for progression-free survival.^[9]

In the phase 2 PALOMA-1 trial reported at the April 2014 annual meeting of the American Association for Cancer Research, the addition of palbociclib to letrozole was shown to significantly slow the progression of advanced cancer (median progression-free survival increased from 10.2 months to 20.2 months), but was not shown to have a statistically significant effect on increasing patients' overall survival times.^[10][11][12]

Pricing[edit]

Ibrance "can be ordered through select" specialty pharmacies and "sells for $9,850 for 30 days or $118,200 for a year's supply before discounts."^[13] According to a statement by the New York–based Pfizer the price "is not the cost that most patients or payors pay" since most prescriptions are dispensed through health plans, which negotiate discounts for medicines or get government-mandated price concessions.^[13] In the United States specialty pharmacies fill prescriptions for drugs that are usually high cost.^[14][15]

References[edit]

1. ^ Jump up to: ^{a b} Finn, RS; Dering, J; Conklin, D; Kalous, O; Cohen, DJ; Desai, AJ; Ginther, C; Atefi, M; et al. (2009). "PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro". Breast cancer research : BCR. 11 (5): R77. PMC2790859 . PMID 19874578. doi:10.1186/bcr2419. 
2. ^ Jump up to: ^{a b} Rocca A, Farolfi A, Bravaccini S, Schirone A, Amadori D (2014). "Palbociclib (PD 0332991): targeting the cell cycle machinery in breast cancer". Expert Opin Pharmacother. 15 (3): 407–20. PMID24369047. doi:10.1517/14656566.2014.870555. 
3. Jump up ^ "FDA Approves Palbociclib for Metastatic Breast Cancer". OncLive. 3 Feb 2015.
4. Jump up ^ "Pfizer Receives U.S. FDA Accelerated Approval of IBRANCE (palbociclib)". Pfizer. 3 Feb 2015.
5. Jump up ^ cite web | url=https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm549978.htm
6. Jump up ^ Late-stage study of expanded use of Pfizer's Ibrance successful; global regulatory applications to follow. April 2016
7. Jump up ^ Finn; et al. (November 17, 2016). "Palbociclib and Letrozole in Advanced Breast Cancer". NEJM. pp. 1925–1936. doi:10.1056/NEJMoa1607303.CS1 maint: Explicit use of et al. (link)
8. Jump up ^ Ibrance (palbociclib) European public assessment report
9. Jump up ^ "Pfizer Announces PALOMA-3 Trial For IBRANCE (Palbociclib) Stopped Early Due To Efficacy Seen In Patients With HR+, HER2- Metastatic Breast Cancer Whose Disease Has Progressed Following Endocrine Therapy". April 15, 2015.
10. Jump up ^ Breast Cancer Drug Shows ‘Groundbreaking’ Results By ANDREW POLLACK, APRIL 6, 2014
11. Jump up ^ Beasley, Deena (6 April 2014). "Pfizer drug doubles time to breast cancer tumor growth in trial". Yahoo! News. Reuters. Retrieved 7 April 2014.
12. Jump up ^ Palbociclib Shows Promising Results in Patients With Hormone Receptor-positive Metastatic Breast Cancer, AACR in the News, April 6, 2014
13. ^ Jump up to: ^{a b} "Pfizer breast cancer drug gets early FDA approval". Daily Mail. London. Associated Press. 3 February 2015. Retrieved 2 November 2015.
14. Jump up ^ Herper, Matthew (19 February 2010), "The World's Most Expensive Drugs", Forbes, retrieved 25 June 2015
15. Jump up ^ Thomas, Kate; Pollack, Andrew (15 July 2015). "Specialty Pharmacies Proliferate, Along With Questions". Sinking Spring, Pa.: New York Times. Retrieved 5 October 2015.

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Categories:

• Piperazines
• Pyridines
• Pyridopyrimidines
• Experimental cancer drugs
• Protein kinase inhibitors
• Breakthrough therapy
• Specialty drugs
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Do you have any information regarding HBOT and concurrent use of chemotheapeutic agents 1) ixabepilone and 2) faslodex?

None of the drugs have a published experience discoverable on a pub med search.

Based on mechanisms of action I doubt any of the drugs wiuld have their toxicities enhanced by HBO2. However, as you know, the decision to treat a patient with HBO2 who is receiving these drugs is the managing physicians decision and our input is meant only to provide guidance based on the information that is discoverable.

Please see the attachment.

Chemotx_and_HBO_3_drugs.docx

What is appropriate for treating patient after seizure in chamber? Should every patient who has had seizure be treated with valium? Is it needed if they are alert/talking after treatments and vitals/glucose is normal?

Our patient was a 91 yr old male being treated for osteoradionecrosis. He had a seizure we believe from possible O2 toxicity. He was being treated at 2.5 ATA for 90 min with one 10 minute air break and pressurization rate of 2psi. Seizure happened minutes after his 10 minute air break. Patient did well with air break (given with mask and air tank gauge showed good respiratory effort).

His seizure lasted for ~30 seconds. He never lost consciousness and was alert and talking during decompression and after removal from chamber. He is not diabetic but did check vitals and glucose post tx and all was normal. Patient also had normal vitals, including normal temp prior to tx.

Our NP examined patient pre and post tx. Patient was outpatient so he went home after tx. We do have standing order that we can give 5mg valium for seizures however NP and myself didn’t think it was indicated.

We would like our policy for possible O2 toxicity to be appropriate so your recommendations would be greatly appreciated. What is appropriate for treating patient after seizure in chamber? Should every patient who has had seizure be treated with valium? Is it needed if they are alert/talking after treatments and vitals/glucose is normal?

The responses to the question varied and therefore rather than consolidating them, we are listing them in order of response. Editor

1. I have a number of comments.  Can you describe this seizure?  Was this a focal seizure without LOC?  I have never seen that during HBO2, but I guess it can happen.  The only ones I have seen were grand mal.  This dose of HBO2 seems a little high for this indication.  Many years ago we went to 2.0 x 90 minutes (at pressure time) for almost all of wound care and radiation injury and still get good clinical outcomes.  Neal authored a letter to the editor in UHM that was convincing that seizures due to HBO2 do not occur at 2.0.  Next, HBO2 may have unmasked an occult seizure disorder. I have seen this several times, in which a patient has underlying brain pathology, including occult seizures (“black out spells” the patient later recalled), so this patient needs to be evaluated for this.  That evaluation typically includes neurology consult with provocative EEG, exam and MRI.  Regarding Valium….If you want seizure prophylaxis for 30 minutes use Valium. If you want it for 2 hours use Ativan.  But before using prophylaxis, it would be prudent to work up the patient first.  I leave the dosing of HBO2 up to that department, but to my knowledge there is no convincing information about 2.5 ATA being superior to 2.0 ATA. LW
   
   
2. Dr. LW "said it all" including questioning the type of seizure, obtaining a neurology consultation, treating at 2 ATA pressures, deferring retreatments until cleared by neurology consultant and use of Ativan rather than Valium. MS
   
   
3. This is a more complicated question than it appears at first glance.  First, I agree that the incidence of oxygen toxic seizures during routine hyperbaric treatment performed at a maximum pressure of 2.0 ATA is vanishingly rare.  There may have been a couple in the history of the world.  This compares to approximately 3-4 in 10,000  routine treatments performed at 2.36 ATA (Welslau 1998, Pflaki 2000, Hampson 2003).
   
   However, the data are not from a population of nonagenarians.  I'm not sure if we know whether the extreme elderly are more (or less) susceptible to CNS oxygen toxicity.  For that matter, I don't think that we know the response rate to HBO2 with regard to angiogenesis in irradiated tissue in patients of this age.
   
   Secondly, to my knowledge, no hard data have ever been published either in human or animal models demonstrating that benzodiazepines are effective in either preventing or aborting oxygen toxic seizures.  When administered prophylactically, it may be a self-fulfilling prophecy because oxygen toxic seizures are so rare, including among patients who have had one previously.  The same goes when administering the drugs to abort an oxygen toxic seizure because the seizure will stop whether you administer drugs or not.
   
   Finally, most oxygen toxic seizures are tonic-clonic, but at least one focal seizure has been reported.  The article is attached. NH
   
   
4. A few points:
   
   (1). Characterization of the seizure is important. If it was a focal seizure at onset, or as evidenced by Todd’s paralysis afterward, then the patient probably has underlying pathology. Seizures due to O2 exposure alone are generalized at onset, not focal.
   
   (2). In our facility we observe O2 seizures even at 2 ATA, although uncommonly. Around 50% of these are due to concomitant hypoglycemia.
   
   (3). Re-institution of O2 after recovery from the seizure rarely causes a recurrent seizure. Nevertheless, many practitioners administer some sort of anticonvulsant, usually a benzodiazepine. When a seizure occurs in a multiplace facility, the optics of restarting the O2 may appear uncaring to other patients. Thus, locking the patient out of the chamber after the seizure has stopped is a common practice, which also allows for closer assessment and appropriate referral. RM
   
   
5. I agree the story is suspicious of something more than a hyperoxic seizure and needs investigation if it was anything but a generalized seizure.
   
   I was interested to hear the other responses and have a couple of comments:
   
   
   1. We also see very occasional seizures but these are (for the last 10 years or so) never associated with hypoglycaemia. That problem seems to have been eliminated with the introduction of an active sugar management program with the diabetic patients.
      
      
   2. We treat as a routine at 2.4 ATA in the multiplace, but after the elimination of a rebreathing phenomenon many years ago, we have come down to a low rate of seizures that we have accepted (right or wrong!). It is about 1:8.000 compressions. I noted Lin's post about treating routinely at 2.0 ATA - we have considered the same but rejected it to date based on the fear we cannot be sure about treatment efficacy given the lower inspired oxygen likely in a multiplace compared to the oxygen-filled monoplace at 2.0 ATA. Perhaps this is illogical and I would welcome more from Lin about how that decision was made. 
      
      
   3. I am very interested to hear that many would prescribe benzodiazepines for someone who has suffered a hyperoxic seizure. This is not our practice and has not been a problem to date - touch wood. In our counselling, we are very keen to distance these seizures from any notion of epilepsy and this includes the benefit of benzos or other anticonvulsants.
      
      
   4. Agree with Richard that it is not a good look to try and put the patient back in the same run. In general, the average hyperbaric patient who suffers a hyperoxic siezure takes some time to recover - rather longer than the classic teaching which is presumably based more on fit young male divers in the Navy than octogenerians with multiple pathologies.... MB

I wanted to ask whether you had any knowledge of clinical circumstances or literature regarding having a patient with a 20+ year old mechanical aortic valve undergo HBO2. The valve has not been pressure tested by the manufacturer?

There are no pressure-sensitive components in a mechanical valve, since it contains no gas pockets. There are no issues with respect to hyperbaric oxygen therapy regarding a prosthetic valve.

My understanding is that air breaks are uncommon anymore in the HBO2 community and I understand that there is a greater risk of O2 toxicity @ 2.4 ATA or greater. Is there any documented evidence for the need of air breaks during the hyperbaric treatments?

Thank you for your question. The UHMS HBO₂ safety committee can provide information to assist you in answering your question, but the ultimate responsibility for these types of questions rests with the medical director and safety director of your facility.

The SC cannot recommend medical practice.  The hyperbaric treatment protocol is the responsibility of the medical director and the safety director.

Air breaks are used in the clinical setting for two primary reasons.  The first to reduce oxygen toxicity involving the central nervous system.  The second is to reduce oxygen toxicity to the pulmonary system. Due to the complexity of our patients and the underlying disease processes, the patient may present with conditions that could possibly lead to a lower threshold limit for oxygen toxicity (i.e. fever, low blood sugars, medications).    

A review conducted in 2003 by Hampson & Atik demonstrated an overall seizure rate of 1 in 3,388 treatments or 0.03% (Hampson & Atik, 2003). In 2011 Banham examined the incidence of oxygen toxicity seizures over 41,273 treatments for 3,737 patients and found the overall rate was 0.06% or 6/10,000 exposures with a higher incident rate in patients treated at increased pressures (0.56% at Navy Treatment Table 6 for dysbarism) (Banham, 2011). Another article reported zero per 10,000 at 2.0 ATA, 15 per 10,000 at 2.4/2.5 ATA and 51 per 10,000 at 2.8 ATA (Heyboer et al. 2014). Patients treated for CO poisoning or decompression illness have an incidence as high as 0.5-2%, presumably due to a combination of CNS injury and higher PO₂ (2.8-3 ATA) used for treatment of those conditions (Hampson et. al. 1996; Banham, 2011). A 2016 retrospective chart review of 2334 patients treated at a hyperbaric center in Israel found a seizure incident rate of 0.3% (7 patients); however, they determined “only one patient (0.04%) had a true oxygen toxicity event” (Hadanny et al. 2016).

Major pulmonary oxygen toxicity has not been reported during routine clinical hyperbaric treatment, although there is a theoretical risk in patients who receive oxygen within a short interval after certain chemotherapeutic agents such as bleomycin and mitomycin C.

The rationale for air breaks is based upon a study in which volunteers breathed 100% O₂ at 2 ATA for up to 19 hours (Hendricks PL, Hall DA, Hunter WL, Jr., Haley PJ. Extension of pulmonary O₂ tolerance in man at 2 ATA by intermittent O2 exposure. J Appl Physiol. 1977;42(4):593-9). Use of 5-minute air breaks after every 20 minutes of 100% O₂ delayed the onset of a measurable reduction in vital capacity (-5%) from 6 hours (without air breaks) to 17 hours. We are not aware of any specific studies that look at the influence of air breaks on CNS O₂ toxicity.  Such a study would be difficult to perform since O₂ toxicity is rare.

Air breaks are prescribed in some standard treatment procedures such as USN Treatment Tables for decompression illness. Routine use of air breaks for other hyperbaric treatment algorithms is at the discretion of the treating physician and is often implemented when treatment pressure exceeds 2 ATA. The time or length of the air break can vary from five (5) to ten (10) minutes (up to 15 minutes for treatment protocols used for decompression illness), typically after 100% O₂ breathing periods of 20-30 minutes.

Banham ND. Oxygen toxicity seizures: 20 years' experience from a single hyperbaric unit. Diving Hyperb Med. 2011;41(4):202-10

Hadanny, A., Meir, O., Bechor, Y., Fishlev, G., Bergan, J., Efrati, Shai. (2016). The safety of hyperbaric oxygen treatment - retrospective analysis in 2,334 patients. Undersea and Hyperbaric Medicine, 43(2): 113-122

Hampson N, Atik D. Central nervous system oxygen toxicity during routine hyperbaric oxygen therapy. Undersea Hyperb Med. 2003;30(2):147-53

Heyboer M, 3rd, Jennings S, Grant WD, Ojevwe C, Byrne J, Wojcik SM. Seizure incidence by treatment pressure in patients undergoing hyperbaric oxygen therapy. Undersea Hyperb Med. 2014;41(5):379-85

DISCLAIMER
Neither the Undersea and Hyperbaric Medical Society (UHMS) staff nor its members are able to provide medical diagnosis or recommend equipment over the internet.  If you have medical concerns about hyperbaric medicine you need to be evaluated by a doctor licensed to practice medicine in your locale, which can provide you professional recommendations for hyperbaric medicine based upon your condition. The responsibility of approving the use of equipment resides with the physician and safety director of the facility.  Information provided on this forum is for general educational purposes only.  It is not intended to replace the advice of your own health care practitioner and you should not rely upon it as though it were specific medical advice given to you personally.

What are the recommendations/contraindications for concurrent HBO and Chemotherapy/Radiation?

This answer is from the recognized physician expert in the field of hyperbaric medicine dealing with oncological disease – John Feldmeier, DO.

“There is no easy answer to this question. We still struggle to answer the question of whether patients with a remote history can have HBO₂.

Although I believe that in almost all cases this would be safe. There is very little published data with concurrent therapy. The issue of concurrent chemo/ HBO₂ has next to no published information and really has become a fairly recent issue because patients are now living longer with active malignancy. There are more and more options for systemic treatment and quality of life issues are pertinent for patients even when they have active disease. The scenario where this becomes an issue is when a patient has had prior radiation, has a complication, needs HBO₂ but is receiving chemo probably because recurrent or residual cancer has been found.

Chemo comes in many varieties with traditional cytotoxic drugs in at least 8 categories and now with more options including immune therapies and anti-angiogenic therapies. It is impossible to make a universal recommendation applicable to all chemotherapies.

Some of these drugs mediate their anti-tumor response through free radicals which cause chemical bond breaks in the DNA leading to reproductive death. Some are antibiotics: some are spindle cell blockers etc., etc. Those that mediate cytotoxicity through free radicals are likely to have their effect enhanced in the tumor and normal tissues.

This was the basis of using HBO₂ as a sensitizer to radiation done from late 50's to early 70's. Since the therapeutic goal is to enhance QOL, this would not be perceived as an appropriate effect.

As I am sure, most of you know Eric Kindwall's book declares there to be a contraindication to Adriamycin and Cisplatin. This precaution is based on pretty weak evidence. On the other hand Dick Clarke has done a preliminary study with colleagues at U of Chicago using HBO2 along with Cisplatin and radiation without signs of increased toxicity.

I am especially concerned about Bleomycin and Avastin. Jake Freiberger, MD of Duke U. has reviewed their experience in treating patients with a PAST not concurrent history of Bleomycin exposure without a demonstrable ill effect. I would not give Bleo concurrently with HBO₂. Avastin and some of the other so called biologics (Erbitux) target growth factors including VEGF to exert their effect. Since we enhance VEGF with HBO₂ are we diminishing the anti-cancer effects of Avastin? Will HBO2 be effective if VEGF is being suppressed by the Avastin? We don't know.

My operational recommendation is: 1)to avoid chemo and HBO concurrently whenever possible.2) If you do give concurrently wait a few half-lives perhaps 4 or 5 to see serum levels significantly lowered before resuming HBO₂ after each chemo administration. Half-lives for all the drugs are published. Avastin is 60 days!! 3) I would avoid Avastin and some of the other biologics as well as Bleomycin as concurrent therapies.“