Hi, my name is Ben Dubois Blanc, I am a professor of medicine and physiology at LSU School of Medicine in New Orleans. I'm in the section of pulmonary critical care medicine. And we're going to review one of the questions that I wrote for SEEK because this question, I think, challenged a few people and offers a lot of great teaching points. So what is the purpose of SEEK and why are we reviewing this question? And I think there are really two purposes of SEEK. One obviously is a board preparation tool. So we want our learners to be able to go into their boards and just nail them. But also I think this is an opportunity for continuing medical education. So sometimes we'll embed in SEEK questions information that just expands your knowledge base about a disease subject, even though it may not actually be testable material. So this is a great question that I think does both. It was challenging to a lot of our learners. We got some really, really good feedback on this question. Some of the points are very, very valid. But I think there's some subtleties in this case that help us choose the right answer. And it really is a nuanced case. And I intentionally made it nuanced to bring out a lot of these important teaching points. So let's go and walk through this case and see what we can learn. This is a case of a young man who was found unconscious. He has a history of heroin addiction. He was last seen well 12 hours before he was found. So that kind of gives us a timeframe for the event. He's found by friends. And then when the paramedics get there, they've got the history. They recognize this as an opioid overdose. And they start giving him naloxone. And it takes three milligrams of naloxone before they can get the patient to arouse. So that tells us right there that this is probably an overdose with either a very large dose of heroin or one of these new fentanyl analogs that's very, very potent. Because it takes a reasonably high dose of naloxone to get arousal. Now in the ED, the patient is satting okay. He's on a 40% face mask. But then he comes up to the ICU 30 minutes later. And although he's easily arousable to voice commands, what do we notice when we look at his vital signs? His heart rate's okay. And he's a little tachycardic. But interestingly, he's only breathing 10 times a minute. And now he's a little bit more hypoxemic than he had been in the ED. And he's coughing up this pink frothy sputum. So I think all of the learners recognize, gosh, this really sounds like this is heroin induced pulmonary edema, opioid induced pulmonary edema. So let's take a look at a coronal slice of his CT, which was figure one. And when you look at this CT, you see kind of a classic radiographic appearance of opioid induced pulmonary edema, which is a kind of a central airspace consolidation with peripheral sparing. So let's go back to the question and see what we're asked about this particular patient. So the question is really what is the most appropriate next step? Now several of the learners said, well, gosh, could this be naloxone induced pulmonary edema? And we'll come back to that question in a minute. Could this be negative pressure induced pulmonary edema potentially? Could this be an aspiration event? Would antibiotics be appropriate here because we think maybe this is an aspiration pneumonia? So the question is really what's the most appropriate next step? And I think the key to answering this question is to go back to the stem and notice that this patient is bradypneic. He's breathing only 10 times a minute. If you had that much edema on your chest x-ray, you'd probably be breathing 35 or 45 times a minute. This patient has respiratory depression from his opioids. So he's still intoxicated. But I think some of the learners were maybe bothered by the fact that he's easily arousable to voice commands. And what's important to recognize is that chronic narcotic use, as opposed to an acute intoxication, allows one to develop tachyphylaxis or tolerance to the depression in mental status. So the effects on the reticular activating system are not as pronounced. You become less sedated, but not to the respiratory depressive effects. So if you actually did blood gases in a methadone clinic, what you would find is a lot of those patients who are walking around talking, many of them working, are actually chronically hypercapnic. So you can have hypercapnic respiratory failure and yet still be wide awake. The most sensitive and specific sign of narcotic overdose is bradypnea. So we can see that this patient is still under the effects of his narcotic. Now some of the learners were concerned, well gosh, if this was naloxone-induced pulmonary edema, am I going to aggravate it by giving more naloxone? And the answer is probably not. That naloxone, when given by continuous infusion and even during the acute resuscitation, was titrated to an effect. So you're going to titrate it to get an improvement in respiratory rate to where the patient is adequately breathing. It would have been nice if I had given you in this question the fact that he was hypercapnic, but that would have made it a little bit too easy. And I wanted you to think more subtly and recognize that bradypnea is a very, very sensitive and specific sign of opioid intoxication. So the correct answer here is to initiate continuous naloxone infusion, titrate it to the effect that you want, which is, in this case, his hypoxemia is getting a little worse. If we'd had a blood gas, he's probably hypoventilating, he might be a little bit hypercapnic, titrate it to the effect you want. Turns out, some of you wanted to initiate mechanical ventilation, but it turns out that only about a third of patients who have opioid overdoses require mechanical ventilation. Some of you wanted to give noninvasive ventilation, which would not have been inappropriate if the patient continued to be hypoxemic. You could recruit up the lung with a little NIV. That was not one of the options that was offered. So an intubation mechanical ventilation really should be reserved for those patients who fail to have an adequate response to a titration of naloxone. Why the continuous infusion? Naloxone is a short half-life, and many of these opioids that are used on the street have much longer half-lives, and this patient is going to start hypoventilating and get back into trouble all over again if we don't start him on a naloxone infusion. So that's the next thing we should do. We would reserve intubation and mechanical ventilation if he had refractory hypoxemia, refractory hypercapnia that we could not control with either naloxone or noninvasive ventilation. So choice A would not have been the next thing that you would have done. Methylprednisolone. Well, methylprednisolone has not been shown to be of help in opioid overdose. It's not been shown to be of help after gastric acid aspiration. So it's not helpful in negative pressure pulmonary edema. So no matter what the diagnosis is in this particular case, methylprednisolone would not have been the correct answer. So choice B is incorrect. What about the administration of systemic antibiotics? Well, if he overdosed, remember he was well 12 hours ago, so he probably doesn't have pneumonia. Could he have aspirated? Sure, he could have aspirated, but antibiotics don't change who among those patients who aspirate who will develop bacterial pneumonia and who will not. So giving antibiotics at this point in time really would not be of any value to this particular patient. So choice D is incorrect. So I think that the most important teaching points of this case recognize that naloxone has a short half-life, that this patient took a big overdose. You're probably not going to hurt him with additional naloxone. In those cases where there has been maybe naloxone-induced pulmonary edema, which is probably much rarer than heroin or opioid-induced pulmonary edema, in those cases it's really with the initial dose that you see the pulmonary edema, not with subsequent doses. So if you titrate it here, you're not going to get that big catecholamide surge. You're just going to improve the respiratory rate and the depth of respiration in this particular patient and improve his gas exchange. Hopefully this pulmonary edema will resolve on its own, maybe with the help of a little diuretic, but within the next 24 hours we would hope that this patient would be better. So recognizing that bradypnea I think was the key to solving this particular question. Thanks guys.

Dr. Ben Dubois Blanc

LSU School of Medicine

opioid-induced pulmonary edema

bradypnea

naloxone infusion