Hello, and welcome to another episode of the TMF Quality Innovation Network’s podcast series on opioid safety in nursing home patients. I’m Dr. Clifford Moy, the behavioral health medical director at TMF Health Quality Institute, a leading non-profit health care consulting organization based in Austin, Texas.
I'm joined by Dr. Paul Milligan, a clinical pharmacist. Today we are speaking about opioid-induced respiratory depression.
Hi. Good morning, Dr. Milligan. How are you today?
Doing well. Thanks for asking me here.
Great. Today, we want to talk a bit about talk about that in a little bit and respiratory depression. We tend to think about that especially in the winter and flu season in patients with chronic respiratory illnesses. What's your experience in that area, Dr. Milligan?
Well, that's especially probably more in the inpatient than the outpatient setting for severe emergent reversal for opioid-induced respiratory depression and falls probably a little more common in the nursing home. But I'll start off with the opioid-induced respiratory depression because I've worked a lot in that area, trying to figure out how do we identify the patients at highest risk for this.
And because we can do extra monitoring, we can use capnography. And who do we use it on? And how do we identify those? So the different algorithms and risk factors span the gamut.
I've seen some that said women were more at risk. I've seen some that said men were more at risk. So that doesn't help us. What comes out top all the time-- almost all the time-- is co-prescribing of other sedating medications with the opioid is a major risk factor and perhaps controllable.
But these drugs are all metabolized. And if you have hepatic or renal failure, you've got sustained use or sustained accumulation of these drugs. And then if you already have some respiratory decline, like sleep apnea or any type of other respiratory dysfunction, your reserve is gone. You don't have much of reserve.
And I think that's why we're probably having a lot of issues with COVID patients is because very obese patients who can't breathe on their back and patients with sleep apnea and COPD are already at risk. On top of that, the FDA has come out with warnings pretty regularly about opiate-naive-- this is a relatively recent one, especially for nursing home patients that talked about opiate-naive patients and patients prescribed these long-acting opioids are at particular risk.
So there's FDA caution I think from this year or maybe within the last year. It may have been a little earlier. But really frail older nursing home residents with renal or hepatic issues have increased risk of adverse reactions, especially when you're starting these long-acting opioids. And we mean bigger doses is also in patients who are getting more than 10 or greater than 20 to 100 milligrams of oral morphine equivalents per day, which isn't too hard to do. Those have an increased risk.
And then again, death from these opioid-induced respiratory events is still more common in younger counterparts than in the older patients, because older patients are not as careless, I guess, if you prescribe them at home, where the younger patients seem to overdose a little more than older ones. So it's a little bit complicated like that. There are a couple of algorithms, if you would like me to go into that to help.
Sure. That sounds like it would be very helpful.
OK. So independent risk factors are mostly what we're looking for. And so age is obviously one. And so there's a trial that we're waiting to see the publication on. They've talked about it in conferences and things like that and kind of told us almost everything we need to know, but not everything is that at least we know what the independent predictors were. And again, this was hospitalized patients getting opioids.
And they looked at patients who had some type of respiratory event, either a low pulse ox or sustained low pulse ox or apnea. And the highest risk was age, older age, greater than 70. Males came out on top here. Patients with heart failure, as you can imagine, already sometimes have respiratory issues.
Patients with sleep disorders and opiate-naive patients-- this is their scoring algorithm. We don't know what the weight is on each of those scores. But those were the five independent predictors of patients who were going to have some type of an event when they were given an opioid. And they monitored them pretty carefully. Again, that's not been published yet, but it seems to make sense and so probably valid predictors.
There's another one that people use periodically. Again, it's called the MOSS-- M-O-S-S-- scale. It's the Michigan Opioid Sedation Scale, I believe. And they found the similar things. They've got sleep disorders. Recent abdominal surgery, again, makes sense because your intercostal muscles are weakened and co-prescribing of any sedative and a previous smoker.
So that's maybe a little bit easier to find out about your patients, if they were smokers or previous smokers or vaping-- go ahead. Or vaping, right?
Yeah, vaping these days.
At our hospital, we came up with one because we wanted to put patients on extra monitoring, which would be capnography on the bedside, not only in ICUs, measuring exhaled CO2. It's a direct measure of ventilation. And we looked every time naloxone was used.
We identified a cohort of patients that had naloxone and needed it-- so not as a diagnostic, but naloxone to reverse their sedation. And we found that over half of our reversals, about 55% of them, were getting parenteral opioid and were already on supplemental oxygen. So if your patient's on the verge of needing supplemental oxygen already, you really want to take a look back at their opioid orders, as well, especially if they're getting these bolus doses.
So again, most of those patients are not sitting at a skilled nursing facility. But the supplemental oxygen masks the pulse ox. It gives you a false sense of security, a pulse ox, if they're getting oxygen.
And learned that from my son, who's a paramedic-- when they put pulse ox and their patients on supplemental oxygen in the ambulance, they discount those. It fakes them out. The pulse ox will be high, but. They're not really breathing, not really ventilating.
Wow, that's an interesting observation. Again, in the COVID-19 world, we're using a lot more pulse ox than we used to use. And think about, again, risk factors that occur-- nursing homes as a potential high-risk environment for COVID-19. Really think carefully and think as a team to look at all of these issues.
You had mentioned some other drug-drug interactions. And one of the drugs that I've always been curious about, class of drugs, are benzodiazepines with opiates. I know that in the community, that seems to be a particularly fatal combination. And in the nursing home, as you mentioned earlier, the number of psychoactive medications that are prescribed has been reduced.
The use of antipsychotic medication is now significantly limited in the nursing home. Are benzodiazepines being substituted in that setting?
And what are the issues with opioids?
Well, yeah, it seems to be. And in nursing homes, I know PRN doses are sometimes out there for anxiety and sleep, drugs related to the benzos. If you have a patient on both-- and again, these are some of the FDA warnings. If you have a patient on both of these drugs, then you really are increasing the risk that they're going to need a reversal.
Just looking at those, it quadruples the risk of a reversal being needed by being on them together. Generally, the Beers Criteria-- most guidelines, recommend that they not be given together. And that's because they work differently. Opioids work in the central nervous system, in the brain stem.
There are mu receptors that opioids work on, and they're everywhere. They're even in the bowel, which is why you get constipation with those. They're also a little bit in the muscles. But benzos by themselves rarely lead to any respiratory depression.
We have benzo overdoses, and we use Romazicon for that. But in combination with opioids, that's when they work by central suppression. They relax the intercostal muscles that I was talking about before. And benzos even reduce the response to carbon dioxide. So you don't even get as strong of a breathing stimulus or take a breath stimulus.
And it's not only the benzos. So Soma and Flexeril, they work by a different mechanism. And they're additive. So you've got any of these things, a multitude of drugs, that when you add them onto an opioid, you have either an additive and sometimes a tragic additive increase in the risk of respiratory depression and breath rate dropping.
Sure. To me, in the past, benzodiazepines and Soma are a really, really dangerous combination. Awful, awful stuff.
I know. And I understand why it's prescribed, because patients who are often bedridden have back issues and back pain and muscle spasms and things like that. But because those work differently to those problems, it just adds on.
Yes. And also, in my experience, patients with COPD that are not oxygenating well tend to be fairly anxious. And I can see that the combination of benzodiazepines and COPD to address the anxiety could really worsen the clinical presentation.
Yes. So there's a kind of a newly emerging drug, I guess, that we're getting more warnings about, gabapentin.
Yes, a very commonly prescribed medication these days for a number of reasons.
Yeah. It works good. But people they're giving it at sleep time and other times. But also, it suppresses different receptors than the opioids do, but in the same areas. And so it's just another one of those additive things. And it's even emerging in the hospital setting. We're realizing it now.
When we evaluate our events, we're finding that a lot of patients are on gabapentin. It's not always a top-of-mind by nurses or providers about the problem. Again, talking about FDA warnings, this one was just eight months ago or so or six or seven months ago, right about the time COVID hit. So it might have not been seen by everybody December 19 of last year.
So what'd it say?
It says that if you give gabapentin with opioids, that there is a co-use, including respiratory depression and opioid overdose. And death occurs. They didn't back off of that. They know new reports are coming into the FDA and ISMP, Institute for Safe Medicine Practices, about it.
But then the FDA backed off a little bit, saying, we don't want to unintentionally increase the use of opioids by turning prescribers away from using this class. So be aware of that, but know that they don't want you to switch everybody over to opioid. But they do know that use of gaba post-surgery is associated with increased naloxone use. So those patients are having those issues. I think it just should raise awareness of that and be cautious.
Is that interaction a combined receptor interaction? Or is it a drug metabolism interaction?
I believe it's a receptor interaction. They just work in different receptors in the same area-- so centrally. I'm not sure which receptors gaba responds to or suppresses, but it's not the mu-receptors. But it's in the same central area to suppress respiration.
Dr. Milligan, thank you for discussing the opioid issue in nursing homes with us today. We wish you well, and we hope our audience has enjoyed this podcast. Thanks again.
My pleasure. Thanks for having me.
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