Undersea and Hyperbaric Medicine Section Newsletter - September 2006, Vol 13, #2
From The Chair
Kevin Ross Hardy, MD
Department of Emergency Medicine
University of Pennsylvania
Greetings from the Section of Hyperbaric Medicine. Time, as always a challenging companion in all our lives, continues on its steady march to an uncertain future. However, wherever challenge exists, there also lies opportunity for positive change. It is with this possibility in mind that I would like to update you all concerning the status of the section goals elucidated in the previous newsletter.
First and foremost, I would like to remind one and all that the Scientific Assembly in New Orleans is rapidly approaching. As you all know, the meeting will include our annual section meeting, which is scheduled for Monday, October 16, 2006, from 4:00 pm – 6:00 pm in room 399 of the Ernest N. Morial Convention Center. I will send another reminder as the meeting date approaches. As usual, that information will also be available as hard copy in the meeting schedule and agenda that you will receive at registration.
The good news is that due to the good offices and contacts of our chair-elect, Sorabh Khandelwal, MD, of Ohio State University, a sponsor has been obtained for the meeting. Accordingly, appropriate refreshments (likely heavy hors’douvres) will be provided to stimulate our discussions and gastric juices. I hope this will provide added impetus for you, our members, to attend and participate. As a reminder, anyone with interest in a more active role in the section is encouraged to consider volunteering as a candidate for the positions of chair-elect or secretary/newsletter editor. Election for these important leadership positions will also occur during the section meeting.
The meeting itself should be stimulating, both academically and practically. Plans are firming for speakers to address both business and academic interests. I would also like to direct your attention to the editorial in this newsletter written by Christopher J. Logue, MD, concerning the January 2005 Cochrane Review, "Hyperbaric Oxygen for Carbon Monoxide Poisoning." This review has engendered responses that may significantly impact the use of our therapy for CO intoxicated patients. I hope to foster a lively debate at the section meeting concerning these issues, possibly leading to a section consensus statement. Therefore, I urge you all to carefully consider the issues involved and come prepared to discuss them.
Along these lines, any member with concerns that seem appropriate for section notice and discussion should contact me directly or through section e-list for consideration of inclusion on the agenda.
Unfortunately, progress toward increasing the strength of our membership has been disappointing. At last count, we have failed to make any progress, and in fact, have lost a little ground. Concerning my personal commitment, I have just about completed my rounds of calls to other programs encouraging new or continued membership and involvement in the section. While reaching the benchmark of a 10% membership increase is certainly in jeopardy, I will continue these efforts down to the wire. Furthermore, I will attempt to contact recently lapsed members to encourage them to re-join our ranks or to determine what factors led to their decision to not renew. Perhaps this information can suggest a course of action for the section to improve retention. I hope to be able to report a late innings rally and last-minute surge toward that goal, much as I hope for a final burst of performance in the wild card race by my beloved but heartbreaking Phillies in the last few weeks of the baseball season. I will report on the outcome of both these quests at the meeting.
Furthermore, I also am unable to report on the development of any new hyperbaric fellowship programs to date. However, I would like to renew my offer to assist any member in the development of a fellowship program proposal or curriculum.
I am happy to report progress toward the goal of improved interactions with the hyperbaric medicine community at-large. I was honored to be elected to the Board of Directors of the Undersea and Hyperbaric Medicine Society (UHMS) as member-at-large this past June. In this position, I will formally liaise with the leadership of UHMS for the next three years, thus bringing that organization’s considerable talent and experience to bear on any shared problems or issues.
Once again, and as always, I encourage feedback and suggestions for ways to improve my service to the section, and for ways to foster its success.
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Join Us for the Annual Section Meeting in New Orleans!
Come hear Allison Stock, PhD, MPH, Toxicologist, Air Pollution, and Respiratory Health Branch, of the CDC present: "Poisoning Prevention During a Crisis: The CDC Investigation and Response to CO Poisoning following Hurricanes Katrina and Rita."
The Hyperbaric Medicine Section will meet on Monday October 16, 2006, from 4-6 pm at the Ernest N. Morial Convention Center, Room 399.
Dinner will be provided courtesy of Ohio State University Comprehensive Wound Center. Please let us know if you are planning to attend. RSVP to email@example.com or call 800-798-1822 ext 3230.
Election of Officers
Election of officers will be held during the section meeting at Scientific Assembly. Nominations from the floor will be accepted for the following offices:
- Secretary/Newsletter Editor
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Editorial: "Evidence-Based Medicine" and Hyperbaric Oxygen Therapy for CO Poisoning: Have we forgotten about the patient?
Christopher J. Logue, MD
In January 2005, a Cochrane Review was published entitled "Hyperbaric Oxygen for Carbon Monoxide Poisoning." This review is a distilled version of an article published in the Journal of Toxicological Reviews (Toxicol Rev. 2005;24(2):75-92). The authors of the Cochrane Review come to the conclusion that "the existing randomized trials do not establish whether the administration of HBO to patients with carbon monoxide poisoning reduces the incidence of adverse neurological outcomes." They go on to write, "Based on the results of these trials, HBO cannot (be) routinely recommended for the treatment of CO poisoning."
There have been many concerns raised about the integrity of this particular Cochrane Review. To begin with, it is extremely unusual for a Cochrane Review not to include a single author who is considered an expert or is board certified in the field of medicine to which the topic of discussion pertains - in this case, hyperbaric medicine and the application of hyperbaric oxygen therapy. Although the lead author of the tox reviews paper is a toxicologist, it is of interest that he practices in a remote location in Australia that does not have a hyperbaric facility nearby. As a matter of fact, if hyperbaric oxygen therapy was indeed considered beneficial in the treatment of CO-poisoned patients, he would have to arrange for his patients to be transferred to one of two facilities: The Prince of Wales Hospital in Sydney (approximately 300 km away) or the Alfred Hospital in Melbourne (some 600+ km away). Interestingly enough, the lead author of one of the clinical trials that showed no benefit for hyperbaric oxygen therapy for CO poisoning works at the facility in Melbourne.
Further concerns have been raised with regard to errors in the review, review author bias, and unprovable claims of a change in primary outcome of the most recent and well-designed trial.
Errors in the Review
The authors of the review have since admitted to misinterpretation of data from an interim report resulting in error with regard to their criticism of one of the positive trials (Thom, 1995). Yet this error will not be corrected "until the next revision" of the Cochrane Review.
Evidence of Bias on Behalf of the Review Authors
Although the authors of the review were exceptionally critical of positive trials, they spent significantly less effort criticizing the negative trial by Scheinkestel, 1999. In fact, although it was of considerably less quality when compared to the positive trial by Weaver, 2002, the two trials were considered equivalent in the Cochrane analysis. In addition, the Cochrane Review states in the "Types of outcome measures" section: "The main outcome measure of interest was the presence of persistent signs or symptoms possibly indicative of neurological injury at follow-up (approximately 4-6 weeks) after randomization." Yet the same authors state in the Tox Reviews article (when discussing the Scheinkestel trial): "The primary outcome of ‘neurological sequelae’ was not based on this smaller group that was followed up for one month, but rather on the neuropsychological test results at the completion of treatment." Based on the Cochrane Review author’s own description of the "main outcome measure" the Scheinkestel trial did not meet criteria to even be included in this review. To make matters worse, one-month follow-up data (with no reference to statistical significance) from the Scheinkestel trial appears in Figure 1 and Table 1. This data has never been published prior to this Cochrane Review.
A change in primary outcome?
The main "issue" the Cochrane reviewers mentions with regard to the Weaver 2002 trial is a supposed change in primary outcome that, according to the Cochrane reviewers, renders the trial insignificant. They accuse the authors of the trial of changing the primary outcome from delayed neurological sequelae (DNS) to six-week neurological sequelae (regardless of whether or not the sequelae were of the persistent or delayed variety). The only evidence they provide as proof of this change in primary outcome is to reference a letter to the editor of the Annals of Emergency Medicine (1995;25(2):271-272), which involves an ongoing discussion specifically about DNS. The context of the discussion appears to have been overlooked by the Cochrane Review authors. In addition, no effort was made to obtain the original study protocol in which the primary outcome was determined at trial inception. Weaver has since responded to this accusation formally on the Cochrane Review feedback Web site on July 3 and has received no official response from the Cochrane Collaboration to date. You can read this feedback at: http://www.cochranefeedback.com/cf/cda/citation.do?id=9531#9531.
What is most perplexing about this sudden "realization" that there is no benefit for hyperbaric oxygen therapy in the treatment of CO poisoning and the tossing aside of a triple blind placebo controlled randomized clinical trial (RCT) published in the New England Journal of Medicine can be tossed aside is that these recommendations are coming from experts in the field of toxicology. Toxicology is a field of medicine where cases are rare and RCTs are few and far between. As a practicing emergency physician, I treat toxicological emergencies every day with therapies (recommended by toxicologists) that have little or no data from clinical trials to support their use. However, in the case of one of the most common toxicological exposures (CO poisoning), we have a treatment (with no other alternative treatments available) that has strong evidence of efficacy as supported by hard data in the medical literature. And now toxicologists are telling me not to use it? I doubt that they would have gone to so much trouble if hyperbaric oxygen therapy were available at every hospital.
Since the publication of this Cochrane Review, practice patterns have been changing, and patients exposed to CO that are at significant risk for neurological sequelae are not being offered hyperbaric oxygen therapy as an option for treatment. Clinicians are referencing this "evidence based medicine" to support their decision to withhold care. We are not doing the best we can for the patients if we join the toxicologists in providing "supportive care" only.
I encourage all of you to examine the literature for yourself. Obtain the references that are cited in the Cochrane Review, and, whether or not you agree with the conclusions, respond to the Cochrane Review formally by going to the Web site that I have previously mentioned: http://www.cochranefeedback.com/cf/cda/citation.do?id=9531#9531.
Our patients are counting on us. Don’t forget about them.
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Christopher J. Logue, MD
Tempel R, Severance HW. Proposing short-term observation units for the management of decompression illness. Undersea & Hyperbaric Med. 2006;33(2):89-94.
Decompression illness (DCI) is a potentially life-threatening disease, often requiring hyperbaric oxygen therapy (HBOT) for symptom resolution. Once treated, current guidelines recommend an observation period of at least six hours for patients with neurological symptoms in case of relapse. Surveys have shown a symptom relapse rate as high as 38.5%, with half of those occurring in the first 24 hours. We propose that a short-term observation unit (OU) would be an ideal setting for these patients to be monitored. To evaluate this, we did a retrospective study of patients presenting with DCI at a major hyperbaric facility. One hundred and two consecutive patients were evaluated with DCI diagnosis and receiving HBOT. Forty-two (41.2%) patients had neurological sequelae; 10 required more than one treatment for refractory symptoms or relapse. Thirty-eight of the 42 patients received up to three treatments, which can be done within the time requirements of short-term observation. We conclude that OUs would provide a safe and efficient disposition for patients after receiving HBOT.
Comment: Observations units have become more common in the world of emergency medicine. This article points out that non-critical patients with DCI are indeed appropriate candidates to be placed in these short-term units to assess for recurrence of symptoms, especially when the patients have been transported long distances to reach the hyperbaric chamber for treatment. The only question is for how long to watch them (6, 12, 24 hrs)?
Thom SR, Bhopale VM, Fisher D. Hyperbaric oxygen reduces delayed immune-mediated neuropathology in experimental carbon monoxide toxicity. Toxicol & Applied Pharmacol. 2006;213(2):152-159.
The goal of this investigation was to determine whether exposure to hyperbaric oxygen (HBO2) would ameliorate biochemical and functional brain abnormalities in an animal model of carbon monoxide (CO) poisoning. In this model, CO-mediated oxidative stress causes chemical alterations in myelin basic protein (MBP), which initiates an adaptive immunological response that leads to a functional deficit. CO-exposed rats do not show improvements in task performance in a radial maze. We found that HBO2 given after CO poisoning will prevent this deficit, but not eliminate all of the CO-mediated biochemical alterations in MBP. MBP from HBO2 treated CO-exposed rats is recognized normally by a battery of antibodies, but exhibits an abnormal charge pattern. Lymphocytes from HBO2-treated and control rats do not become activated when incubated with MBP, immunohistological evidence of microglial activation is not apparent, and functional deficits did not occur, unlike untreated CO-exposed rats. The results indicate that HBO2 prevents immune-mediated delayed neurological dysfunction following CO poisoning.
Comment: This article provides more basic science evidence to support the role of hyperbaric oxygen therapy in the protection of neurological injury from CO poisoning.
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From the Fellows
A 34-year-old commercial diver with visual changes and headaches after diving: the conclusion.
In the last issue of the Hyperbaric Medicine Section newsletter, we presented a case of a commercial diver who was referred to our hyperbaric facility for the evaluation of his recent symptoms that included visual changes and headaches that always occurred approximately 2 hours after surfacing from long shallow work-related dives. He also had a history of decompression sickness (DCS) treated twice with hyperbaric oxygen therapy in the past. When last we left you, we asked the following questions:
- What is your differential diagnosis?
- What diagnostic work-up would you include?
Here is the rest of the story.
- Referral to neuro-ophthalmology for consultation and review of MRI/MRA.
- Referral to cardiology for consultation.
- Bubble echocardiogram ordered to screen for a patent foramen ovale (PFO).
- Bubble echocardiography revealed a moderate sized patent foramen ovale with significant shunting of bubbles during valsalva maneuver.
- Neuro-ophthalmology consult gave an impression of a migrainous process, and an association with the PFO was suggested.
- Cardiology consult confirmed the diagnosis of a patent foramen ovale. Given that the patient depends upon commercial diving for his livelihood, and at the patient’s request, surgical closure of the PFO was recommended.
Intervention and Follow-Up
- The patient underwent percutaneous closure of his PFO by interventional cardiology using a 33mm Cardioseal device.
- Following his PFO closure, he was placed on 81 mg aspirin and 3 months worth of Plavix 75 mg daily. He was also instructed that he will require antibiotic prophylaxis for life for procedures.
- After 3 months he was medically cleared to return to commercial diving. During the past 7 months, he has been actively commercial diving with no recurrence of symptoms.
Decompression induced migraine headaches associated with a patent foramen ovale.
PFO and DCS
It has been established in the literature that there is a higher prevalence of PFO with shunting in populations of divers with a history of DCS (49% - 61%) when compared to divers without a history of DCS (5% - 19.8%) and to the normal population (27%). A recent meta-analysis from several papers that reported on PFO in divers reveals an odds ratio for developing any form of DCS at 2.5 (CI 95%, 1.4-4.2) for divers with a PFO.
Official recommendation of surgical closure of a PFO in a diver who has suffered from DCS remains controversial. The risk/benefit ratio must be carefully considered.
PFO and Migraines
Several studies have shown that the prevalence of PFO and right-to-left shunt in patients with migraine headaches is significantly higher than in patients without migraine. Also, among patients with a PFO, migraine with aura was 3.5 times more prevalent than subjects without PFO.
A recent meta-analysis has shown that intra-atrial abnormalities [PFO and atrial septic deficit (ASD)] are risk factors for cryptogenic stroke (ischemic stroke in patients less than 55 yrs old without an identifiable cause).
In addition, there are now several case-control studies supporting transcatheter closure of ASDs as a therapeutic option for migraine headaches. These studies show a dramatic decrease in the incidence and severity of migraine symptoms after closure of the shunting defects.
Nevertheless, official recommendation of surgical closure of a PFO in a patient suffering from migraine headaches also remains controversial.
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