COPD: Is EMS Killing Patients with Oxygen? (2)

The Tasmanian Study
Disclosure - the lead author used to be my partner. We were both medics at the same two agencies (volunteer and hospital) in New Hampshire. He never seemed to run out of energy, and it doesn't seem like that's changing!

And since we're talking about Tasmania, we might as well get this out of the way...

Dr. Austin at work.

Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial was well done, especially for EMS research. It's unfortunate that the bar is so low in our corner of health care research, but Austin et al. are working to change that.

The study utilized an EMS service that covered both rural and urban settings, but transported to only one hospital. Paramedics were supposed to identify patients with "breathlessness and a history or risk of COPD," and enroll those patients that they suspected of having an acute exacerbation of COPD.

Most of the treatment was the usual stuff - salbutamol (aka albuterol), ipratropium, dexamethasone, etc. CPAP was not available. The only difference had to do with how oxygen got delivered.

Prior to treatment, patients were randomized to receive either titrated oxygen, delivered by nasal cannula to maintain a sat around 90%, or high-flow oxygen, administered by NRB mask.  Transports lasted an average of 45 minutes, and then the folks in the ED treated as they saw fit.

Before we look at the results, you have to understand two huge issues:

• Only about half of the patients had pre-existing COPD, as judged by a pulmonologist. There's no description of what the rest had. Perhaps many of them had a new diagnosis of COPD, while others where actually pneumonia or CHF with wheezing.
• There were a lot of protocol violations: 56% of the titrated-oxygen group got high-flow oxygen, while 21% of the high-flow group didn't get high-flow.

With those facts in mind, they found:

Note how the results are broken down by all patients versus only those patients with previously confirmed COPD. The most important result is that there's a 5% difference in mortality for all of the patients.

So, what's the problem? It seems to be pretty clear evidence that paramedics should be withholding oxygen in suspected COPD exacerbations, but there are a few reasons why we should be cautious in using these results on the streets tomorrow.

1. The results seem almost too remarkable to be true.
They show 5% increase in mortality between the high-flow and the titrated oxygen groups.  That's a "number needed to harm," or NNH, of 20. In other words, for every 20 patients you give a NRB to, 1 will die.

That's a really high number! Usually you have to do a lot of work in medicine to show that kind of effect. For example, you have to treat 20 STEMI patients with aspirin and streptokinase (versus placebos) to save one life.

And you know all that fuss about rushing the STEMI patient into the cath lab? We have to treat 50 STEMI patients with angioplasty (versus thrombolysis), to save 1 life.

Given this context, the result almost seems "too good to be true." Given that there is little randomized controlled data out there with similar results, and given the good-quality data that conflicts with it (as with the ICU studies described in the prior post), it is reasonable to be skeptical about the conclusions, and await validating data.

2. The oxygen therapy was brief.
The intervention only lasted during transport, on average about 45 minutes. Compare that with the Gomersall study in my last post, where patients in the ICU received higher levels of oxygen for 2 days. While certain brief EMS interventions can have important long-term consequences (defibrillation anyone?), the onus is on the authors to make the case that it was solely the EMS intervention that differed between the two treatment groups. They concede that it was difficult to isolate the effect of the EMS intervention, and state that:

"Unfortunately, collection of data on in-hospital management was beyond the scope of the study, so we cannot dissect the effect of prehospital and in-hospital oxygen administration."

3. Paramedics don't treat "confirmed" COPD
Although withholding oxygen in the cases of "confirmed" COPD looked very effective, the unfortunate truth is that paramedics apparently misidentified half of the patients as COPD.

Now, this may not be entirely true. Some of the "non-confirmed" cases may have been a first-time COPD attack, and the medics were spot on. Or, perhaps some of the cases were actually, say, CHF, or pulmonary emboli. We aren't given any data on what this sizeable subgroup was ultimately diagnosed with.

Remember, though, that most other causes of hypoxia are treated with oxygen. With that in mind, we are left to consider the effect on mortality for the patients who did not have COPD. It does not seem likely that their treatment was improved by leaving them hypoxic.

By the way, this is the same reason you don't treat "hyperventilation" with a paper bag. Seriously, you aren't doing that, are you?

"Med control, we have a problem."

4. There was no difference in rates of mechanical ventilation.
In general, it's hard to show a difference in mortality for any given therapy, because deaths are far less frequent than other bad events. For instance, you need to treat 13 patients in CHF with non-invasive positive pressure ventilation (NIPPV) to prevent 1 death, but you only have to treat 8 patients to prevent an intubation (figures from The NNT).

In fact, we also know that NIPPV cuts the rate of mortality of COPD exacerbations by about 42%, but drops the intubation rate more, by 52%.

So it's kind of odd to see this profound difference in mortality, but no difference in the rates of mechanical ventilation. Similarly, there's no difference in the average length of hospital stay here, another sensitive measure of the effectiveness of a therapy.

5. Oxygen is not the issue.
Ultimately, the study is not asking a relevant question. We know that COPD is primarily an issue of impaired ventilation, and that NIPPV is the treatment of choice for severe exacerbations, along with steroids, bronchodilators, and antibiotics.

In a way, designing a study that only looks at levels of oxygen delivery in COPD exacerbation is sort of like designing a CHF study that only focused on fluid restriction, but didn't use nitroglycerin or NIPPV.

Yes, it would probably show a benefit of fluid restriction, but that's not the problem!

The Bottom line

1. Suppressing the "hypoxic drive" is a rare entity, and concern for it should not drive management.
2. Withholding oxygen could be very dangerous if you are wrong about the diagnosis.
3. Treat bad COPD with bronchodilators, steroids, antibiotics, NIPPV, and, if hypoxic below their baseline, oxygen. Intubate PRN.
4. We're looking forward to more high-quality studies from Tasmania!