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!

COPD: Is EMS Killing Patients with Oxygen? (1)

So this was one of the first bits of medical "lore" I learned as a spanking-new EMT-B. ("Lore" meaning things that are not found in textbooks, but that everyone knows are true.) You don't give oxygen by NRB to a COPD patient.

And you always leave a note. (Hurry up Netflix!)

Well, it turns out a lot of things I learned at that time have been discarded; MAST pants, the EOA, the long spine board (soon, soon...). How has high-flow oxygen fared?

Are we killing patients?

A recent study suggests that the old-time myth was true. In fact, if this study is corroborated, we may need to change our practice somewhat. The one-sentence summary of Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial is:

For high flow oxygen treatment in patients with confirmed chronic obstructive pulmonary disease in the prehospital setting, the number needed to harm was 14; that is, for every 14 patients who are given high flow oxygen, one will die.

That's a really high number.

By comparison, when we rush a STEMI patient to the cath lab, or give then thrombolytics, we have to treat 50 patients to save one life. This study suggests that we can save far more lives by using a nasal cannula instead of a face mask. Can this be true?

Let's first take a look at some older evidence, giving us some context. In the following post we'll go over the new article that has generated so much interest, and see if some practical conclusions can be drawn.

Two ICU studies
The authors of Influence of inspired oxygen concentration on deadspace, respiratory drive, and PaCO2 in intubated patients with chronic obstructive pulmonary disease wanted to study this (possible) myth of the hypoxic drive. They studied the effect of increasing oxygen delivery to a very sick bunch of COPD-ers, 12 patients who had already been intubated after a bad COPD episode. These patients were just starting to recover, being weaned from the vent, able to breathe or their own, and were likely to be extubated in the next day or so. 

The researchers bumped up the oxygen level to 70% for 20 minutes, and checked what happened with the vent and the blood gas. Although 70% doesn't seem high, it is actually right about what we are delivering with a standard non-rebreather mask at 15 lpm (See Weingart's article for explanation; PDF if you prefer).

So what happened? Apnea? Bradypnea? Failure of the hypoxic drive????

They, uh, got more oxygen. That's it. In this population of sick-sick-sick patients, nothing happened.


Okay, you say, perhaps they were a delicate population, but they had been getting beta-agonists and steroids, and probably antibiotics for a few days. That's the whole reason, after all, that they were being weaned off the vent - they were now better. 

Maybe we should instead look at patients who are not yet intubated, but might be if just one more thing tips them over.

"Our study included one patient - this guy"

So, back to the ICU. The authors of Oxygen therapy for hypercapnic patients with chronic obstructive pulmonary disease and acute respiratory failure: a randomized, controlled pilot study. looked at patients right on the brink, with PaCO2 > 50 mmHg, and PaO2 < 50 mmHG - members of the 50/50 club! They were not yet intubated, but it could go either way.


The investigators titrated oxygen up with Venturi masks to two different levels, either a PaO2 of > 50 mm Hg in 17 patients, and > 70 mm Hg in another 17 patients. They got all all the usual meds, of course. As expected, some of these very sick patients had to be intubated, and some even died. The rates of intubation and death, however, were the same in each group. And no CO2 retention either!

So why all the fuss? As an editorial in Critical Care Medicine pointed out, the main evidence for the harm of oxygen in COPD exacerbations comes from the 70s, a time before noninvasive ventilation, routine steroid use for COPD, and even Atrovent was barely a year old! Another editorial from the same journal lays into the medical-education complex for perpetuating this lore:

"One sample of medical mythology is the commonly told story that the administration of oxygen to a patient with chronic obstructive lung disease will shut down the patient's hypoxic respiratory drive and lead to apnea, cardiorespiratory arrest, and the subsequent death of the patient. ... It is not clear where this fallacious information comes from, but it seems to enter the medical information database at an early age, at the medical student or resident level, almost like a computer virus corrupting the appropriate function of the equipment. In addition, this myth becomes very difficult to extinguish during the career of the physician, even with clear factual information of long standing. The danger here is that this medical mythology will inappropriately influence treatment decisions in patients."

The Bottom Line
This is hardly a comprehensive review of all the literature out there on the topic, but most of the other studies are observational, and it's really hard to draw firm conclusions from that sort of data. I haven't bothered to review them here, because why waste our tine if higher-quality studies have been done?

With this background, I'll discuss the important EMS study from 2010 in the next post.

STEMI with a twist... and then a second twist!

This would make a lousy case for a EMS 12-Lead-style presentation, because it's a little to difficult to predict the outcome. And I can't really find a new EMS study, or even an old one, to present with this. If there is any lesson to learn from this case, it would have to be: patients will keep you humble.

The Patient
The history was a little iffy, as the patient was elderly and had a history of both CVAs and dementia, and was variably describing either a week of chest pain or "Nothing! I'm fine!"

EMS had called with a STEMI, though, so I met the paramedics at the ED door, and they handed me the ECG:

You know, they say "treat the patient, not the monitor," but when this shows up on the monitor, you treat that.

We grabbed another ECG after cards had been called for the cath lab activation:

By the way,  I know some sharp readers out there are already asking for right-sided leads, but V4R didn't reveal too much. But even without that, one could make a stab at guessing the infarct-related artery - it seems sort of classic. The STE in III versus aVF, the depressions in aVL and I, not to mention V2, all pointed to an RCA lesion. Intern stuff.

And then the cards fellow asks me if I've seen the patients old ECG. Oh, give me a break...

Twist #1
Now, I almost always check the old ECGs before I call cards, but in this case I was wondering how the old ECG could possibly be relevant to this clearly acute ischemia...

Ah. I see.

This ECG was recorded a number of months prior. The patient, at that time, had been brought to the hospital for another medical emergency, and was incidentally found to have an apparent STEMI. The catheterization revealed a totally occluded RCA, likely chronic.

"What a twist!"

Sooo, no cath then?

Despite the vague history the patient provided, it seemed consistent enough with AMI. There was also some concern that the collaterals that were serving her right ventricle might have acutely occluded.On top of all that, the deep drop in her blood pressure (thankfully transient) after I gave her nitroglycerin seemed to confirm the ECG. Off to the cath lab she went, leaving me feeling only somewhat less sheepish.

Twist #2
And the infarct related artery was...

"Ta-da!"

The LAD.

A "hazy appearing" lesion was visualized fairly proximally in the LAD, just before the first diagonal. Just to be sure, they used the intravascular ultrasound to confirm the freshly-ulcerated plaque, and put in a few stents. All better!

Follow-up
Well, not really. Our patient suffers from "multiple comorbidities," and did not tolerate the procedure so well. A ballon-pump was placed to support her hypotension during the procedure, and during her subsequent hospital stay any number of issues have popped up; bleeding, sepsis, renal stuff.

And her current ECG, a month later?

Huh.

Bottom line
Stay humble. I like to think that I've gotten pretty good at guessing the culprit artery in STEMI, but I was out of my depth on this one!