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Toxicology Rounds: Delving into the Evidence for HBO, Opioids, and Blockers

Gussow, Leon MD

doi: 10.1097/01.EEM.0000443924.91971.60
Toxicology Rounds

Dr. Gussowis a voluntary attending physician at the John H. Stroger Hospital of Cook County in Chicago (formerly Cook County Hospital), an assistant professor of emergency medicine at Rush Medical College, and a consultant to the Illinois Poison Center. He is also the editor of his own blog, The Poison Review.





The 2013 Scientific Assembly of the American College of Emergency Physicians in Seattle had a number of sessions devoted to poisoning and toxicology, but the ones on hyperbaric oxygen, the prescription opioid epidemic, and the differential for hypotensive, bradycardic patients were most interesting to me.

Does hyperbaric oxygen significantly improve clinical outcomes in carbon monoxide toxicity? Proponents and skeptics debated the value of hyperbaric oxygen (HBO) therapy for carbon monoxide poisoning and the quality of the medical literature addressing it in a lively, contentious session that at times resembled CNN's “Crossfire.”

On the pro-HBO side were Tracy Leigh LeGros, MD, PhD, the director of the undersea and hyperbaric medicine fellowship at Louisiana State University, and Stephen Thom, MD, PhD, the chief of hyperbaric medicine at the University of Pennsylvania. Representing the skeptics were William Mallon, MD,from the University of Southern California, and Jerome Hoffman, MD, from UCLA.

The proponents based much of their argument on the paper by Weaver et al, which Dr. Thom called the best published study to date. (N Engl J Med 2002:347[14]:1057.) That investigation of 152 patients with symptomatic acute carbon monoxide poisoning who were randomly assigned to receive three sessions of HBO or one session of normobaric oxygen (NBO) plus two sessions of normobaric room air. All sessions took place in a monoplace hyperbaric chamber in an attempt to minimize bias.

The authors concluded that three hyperbaric-oxygen treatments within a 24-hour period appeared to reduce the risk of cognitive sequelae six weeks and 12 months after acute carbon monoxide poisoning. Dr. Hoffman countered that the study was seriously flawed because the improved outcomes in the study group might have come from the increased duration of oxygen therapy, not the pressure under which the oxygen was delivered.

Drs. Hoffman and Mallon thought that a far better study was done by Scheinkestel et al at Alfred Hospital in Melbourne. (Med J Australia 1999;170[5]:203.) That trial randomized 191 patients to receive HBO for 100 minutes on each of the first three hospital days (HBO group) or similar sessions with normobaric oxygen (control group). All sessions in both groups took place in a multiplace chamber.

Patients still symptomatic after three days received an additional three days of HBO or NBO. Significantly, all patients in each group received high-flow oxygen between treatments. The chief outcome measurement was performance on neuropsychological tests when treatment was completed and at one month. The authors concluded that HBO therapy did not benefit and may have worsened the outcome. “We cannot recommend its use in CO poisoning,” they wrote.

Dr. LeGros vigorously attacked the Scheinkestel paper on many fronts, including the disappointing one-month follow-up rate of only 46 percent and possible incomplete data reporting. Most convincingly to my mind, she pointed out that the paper's protocol did not in any way reflect reality because no one routinely treats victims of carbon monoxide poisoning with three to six days of continuous high-flow oxygen.

The debate reinforced my belief that none of the CO literature is all that convincing, and that, as Dr. Mallon remarked,we probably would have seen clear evidence by now if HBO significantly improved patient outcomes in important ways.

One additional note: I listened to the debate again online, and took ACEP's CME quiz. One of the questions was:

Which study is considered the most well done randomized controlled trial on the use of hyperbaric medicine for carbon monoxide poisoning:

  1. Mathieu, 1996
  2. Weaver, 2002
  3. Annane, 2011
  4. Scheinkestel, 1999

The only answer accepted was “Weaver, 2002,” which is totally outrageous and biased. The question was obviously written from the point of view of the HBO aficionados, who represented only one side of the debate. As the entire session demonstrated, all of the large studies on the use of HBO to treat CO poisoning have serious problems, and there is clearly no consensus on which, if any, is the best.

Prescription opioid epidemic: William Hurley, MD, the director of the Washington Poison Center, noted the increase in the number of deaths from prescription opioids since the mid-1990s, and he has tracked the increase in prescriptions written for opioid analgesics over that period. The trend began at the same time drug companies began aggressively marketing preparations such as OxyContin, and pushing the campaign to make pain a “fifth vital sign.” Today, prescription opioid overdose is the leading cause of accidental death in the United States. Some studies suggest that emergency practitioners prescribe up to 50 percent of the drugs responsible for these deaths.

Dr. Hurley made some important and not-so-obvious points. Among them:

  • Many patients who overdose on prescription opioids are using them not as analgesics or to get high but to treat underlying comorbid conditions such as anxiety or depression.
  • It is prudent to assume that an ED patient who wakes up after receiving naloxone has taken long-acting methadone and needs to be admitted for prolonged observation unless the presence of methadone can be ruled out with a specific drug test.
  • Several areas, including King County, WA, have succeeded in reducing prescription drug overdoses and deaths,but this has often been followed by an increase in the incidence of heroin overdoses.

Differential diagnosis in the hypotensive, bradycardic patient: Steven Bird, MD, from the University of Massachusetts Medical School, gave an excellent lecture called “Cutting Edge Ideas in Toxicology.” He mentioned several topics, but most interesting to me was patients poisoned by beta-blockers or by calcium channel blockers who present with low blood pressure and low heart rate. Check the serum glucose and the patient's skin to tell these two toxicities apart. Beta-blocker overdose tends to present with low or normal glucose and cool skin. A high serum glucose (especially in a patient who is not diabetic) and warm skin strongly suggest calcium channel blocker overdose.

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