Transcript
Speaker: Welcome to Critical Matters, a sound critical care podcast covering a broad range of topics related to the practice of intensive care medicine.
Speaker: And now, your host, Dr. Sergio Zanotti.
Speaker: It is common for patients who were poisoned or have overdoses under different circumstances to be admitted to the ICU.
Speaker: There is a wide range of clinical syndromes caused by overdoses that lead to critical illness.
Speaker: This episode of the podcast is the first of two-part series on toxicology in the ICU.
Speaker: Today, in Part 1, we will cover the general approach to treatment, and in a future episode, Part 2, we will dive deeper into specific toxins.
Speaker: Our guest is Dr. Gerald Lakin.
Speaker: Dr. Lakin is currently the Director of Medical Toxicology at North Shore University Health System, Omega, which includes several hospitals in Illinois.
Speaker: He is Associate Director of the Toxicon Consortium based at John H. Stronger Hospital of Cook County in Chicago.
Speaker: In addition, he is a Clinical Professor of Medicine at the Pritzker School of Medicine, University of Chicago, and Professor of Medicine and Pharmacology at Rush Medical College.
Speaker: Dr. Lakin has published extensively in the field of toxicology and is an active toxicologist in clinical practice.
Speaker: Finally, Dr. Lakin was one of my attendings during Residence and Fellowship.
Speaker: I would be remiss not to take the opportunity to thank him for all he taught me and especially for doing it always in the most supportive and encouraging way.
Speaker: Thank you, Jerry, and welcome to Critical Matters.
Speaker: Thank you very much for inviting me.
Speaker: So I think that I would like to start with maybe getting some definitions clear.
Speaker: When we search for overdoses or poisoning or intoxications, people use all these terms like overdose, toxic ingestion, or poison interchangeable.
Speaker: Does it really matter?
Speaker: Are they different?
Speaker: I believe they are.
Speaker: First of all, the definition of overdose that we usually follow is an excessive dose at which there is no expected therapeutic benefit.
Speaker: For example, if someone takes five aspirin, that is an excessive dose, but there is some benefit to taking five aspirin.
Speaker: The risk certainly may not be worth the benefit, but there is some benefit.
Speaker: There's absolutely no benefit to taking 50 aspirin or 100 aspirins in a sense.
Speaker: So that's an overdose, is where there is no expected therapeutic benefit, which is due to an excessive dose.
Speaker: Toxic congestion.
Speaker: is essentially an ingestion that can produce an adverse effect that's almost a definition of toxicology in general which is a study of drugs or chemicals which can produce an adverse effect in humans intoxication is and usually a nervous system abnormality due to a drug or toxin such as alcohol inebriation is
Speaker: is inability to perform acts of daily living or activities of daily living due to a drug or toxin.
Speaker: For example, if someone is passed out due to alcohol, that's inebriation and probably alcohol intoxication, but more specifically, inebriation, as opposed to a functioning drunk who's walking and talking that is intoxicated with alcohol, that's intoxication.
Speaker: And when do you use the word poison?
Speaker: Does that have to do with the intent or not necessarily?
Speaker: Not necessarily.
Speaker: It could be an accidental poisoning per se in the sense, but it's similar to intoxication in that it's an adverse effect due to a dose-effect relationship from a drug or toxin.
Speaker: So I think that for the rest of the podcast, we'll probably use some of these terms.
Speaker: Hopefully, I'll use them appropriately.
Speaker: But really, what we're talking about is the injection of a drug or chemical that has produced toxicity.
Speaker: So toxic ingestions would be kind of the overarching theme, I guess, for the rest of the conversation.
Speaker: Could you start, Jerry, with telling us, giving us a general overview of what are the numbers like in terms of toxic ingestions in the U.S. for people, for adults requiring further medical treatment?
Speaker: Certainly, Sergio.
Speaker: Well, first of all, toxicology is one of the very few fields in medicine that's centralized.
Speaker: We have a set of poison centers, 55 of them in the United States, that all feed their data into one place.
Speaker: And so every call into a poison center is computerized.
Speaker: And all calls to the poison centers are essentially followed up within 48 hours.
Speaker: So we have a database.
Speaker: of approximately two million exposures nationally per year over the past 30 years in this sense.
Speaker: So that's the number of calls.
Speaker: They're called into poison centers yearly.
Speaker: It's approximately, actually in the year 2017, it was 2,115,186,000 human exposures, which comes out to approximately 6.4 per thousand population.
Speaker: And among those, yeah, go ahead.
Speaker: I was just going to say about a million of those were pediatric exposures.
Speaker: Okay.
Speaker: And among those, what would be the most common toxins in adults and what are the ones that are most dangerous or most likely to cause death?
Speaker: Well, the top five human exposures overall are analgesics, accounting for about 11% of all causes and poison centers.
Speaker: Household cleaning substances, about 7%.
Speaker: Cosmetics, about 6.5%.
Speaker: sedatives, antipsychotics, hypnotics, and antidepressants, they round out the list of top human exposures.
Speaker: For top five or six common calls, age under five years old, they run into cosmetics, household cleaning products, analgesics, foreign bodies or toys, or ingestion of topical products.
Speaker: Now, as far as fatalities go,
Speaker: 86% of all deaths are due to pharmaceuticals called into poison centers.
Speaker: And these involve sedative hypnotics, cardiovascular drugs, of course, the opioids, stimulants, analgesics, and antidepressants.
Speaker: And I think it's important to emphasize that, even though some of these obviously might be prescription medications, they are widely available in many households.
Speaker: And that's why probably the numbers are so high, like you mentioned earlier.
Speaker: That's true.
Speaker: That's exactly true.
Speaker: So you talked about the centralized nature of the practice of toxicology, and I think that this would be a good place to maybe, if there's anything that people take home, is that when they have a suspected toxic ingestion, they can call a poison center and get help, correct?
Speaker: 1-800-222-1222.
Speaker: That's a line, if you call it any place in this country, you'll be sent to the local poison center.
Speaker: Because one other aspect that people don't realize is that Poison Center is the first line or front line agent for what we call toxico surveillance.
Speaker: That is that all this data that we get through the Poison Center, all these calls are uploaded to a national database every eight minutes, which is astounding if you think about it.
Speaker: So therefore, we can tell if an epidemic is occurring, if an unusual cluster of overdoses or toxicities are occurring within an hour or two.
Speaker: This helped us as far as last year with the synthetic cannabinoid occurrence that was contaminated with prodificom, which is a rat poison, and that caused bleeding, of which I believe up to date there are about four deaths associated with it.
Speaker: But we were able to identify it literally within hours of these calls being called into the poison center.
Speaker: Had there not been any poison center, the correlation to this agent might have been very difficult to take and take weeks or months to try to secure this association overall.
Speaker: But we were able to associate it within literally hours.
Speaker: And I think that that's a very important point that many of our listeners might not be aware.
Speaker: So it's not only that as a provider or physician that taking care of possible toxic syndrome that you can get help from a poison center, but you have a responsibility to sharing information, especially when there's maybe a weird uncommon presentation because it might be part of a bigger cluster that's affecting other patients.
Speaker: And without that information, it becomes very difficult to identify that.
Speaker: Exactly.
Speaker: We often contact the CDC or the local boards of health or the local public health departments for these issues, also to try to secure appropriate antidotes that may be rarely available, in addition to coordinate the care, to standardize the care, so to speak.
Speaker: And we can offer also some places in which these patients can be referred to.
Speaker: So I'll include that.
Speaker: I'll repeat that number.
Speaker: 1-800-222-1222 is the poison center for all the country.
Speaker: Correct.
Speaker: So let's talk a little bit about diagnosis, Jerry.
Speaker: And I think that one of the difficulties with toxic ingestions is that a lot of times these patients come with nonspecific findings and it has a very broad differential.
Speaker: They don't always come with an empty box or bottle of pills and saying, I took all this.
Speaker: So what are some of the symptoms or presentations that should prompt a physician or a care provider to think about a possible toxic ingestion or toxic effect?
Speaker: Well, certainly certain symptoms that occur suddenly in an individual that's previously healthy should be
Speaker: be a consideration such as muscle rigidity or seizures or delirium nystagmus especially if it's rotatory nystagmus that could be a clue for a toxic congestion obviously blood pressure changes and unexplained cardiac arrhythmia acute liver or renal failure in the sense electrolyte abnormalities particularly with glucose sodium and potassium
Speaker: And one of the basic things that we look at, of course, are anion gap acidosis, osmolar gap.
Speaker: And one of the other important aspects that we see in overdose patients or toxic patients as a manifestation of toxicity is non-exertional or non-exercise-induced rhabdomyolysis.
Speaker: So these are some of the important clues of an individual taken in a substance that can cause these major problems.
Speaker: And I think that also another area where toxic ingestions or toxic effects of medications is very prevalent is in our elderly population, especially those who are institutionalized, where there seems to be an increasing number of medications that people get, polypharmacy, and they come with a
Speaker: with a very low cognitive baseline and now there's a change in mental status and we really don't have a good opportunity to get a good history, I presume that that's a population that's at high risk as well, correct?
Speaker: Yes, and those can be some of the most difficult things to evaluate and to discover what the etiology is.
Speaker: Because oftentimes, as you stated, it's multiple drugs, polypharmacy,
Speaker: And therefore, the individuals don't present with the classic what we call toxidrome, which is a group or pattern of signs and symptoms associated with a particular class of substance, such as hot as a hair, red as a bead, mad as a hatter.
Speaker: That's the anticholinergic toxidrome.
Speaker: When we're talking about the elderly, it's usually polypharmacy.
Speaker: And so the physical exam won't really give you as many clues as with a younger individual that just took one drug.
Speaker: So you mentioned the word toxidrums, and I was going to ask you, is this something that, as a toxicologist, you find practical, or is it something that we study for boards?
Speaker: Well, it's a little bit of both, but it's very practical, especially in the pediatric ingestions.
Speaker: It was a term coined by Howard Mopfison back in 1970, the Pediatric Clinics of North America, and he coined this term to determine the pattern of symptoms or signs due to specific substances.
Speaker: the cholinergic signs for example as salivation lacrimation urination defecation GI signs emesis these group of signs and symptoms they're pretty reliable for single ingestions and of course one of the most important things we look at is pupil size meiosis versus medriasis and especially with medriasis for example for the sympathomimetics such as amphetamine and cocaine
Speaker: individuals may have dilated pupils as they do with anticholinergic agents such as antihistamines but with anticholinergic agents the pupils do not respond to light whereas with the sympathomimetics such as cocaine they do respond to light so these are important clues that can give an idea of even though the other symptoms may be similar these are important clues that we can differentiate what the drug classification is and it is a whole concept of
Speaker: that it's important to know what the drug classification is.
Speaker: It almost doesn't matter if it's diphenhydramine or dioxillamine.
Speaker: They're both antihistamines.
Speaker: They're both treated pretty much the same.
Speaker: So in this sense, it's important to know the drug classification.
Speaker: So I think that just for a review for some of our audience, can we just go over the basic toxidrome?
Speaker: So you already mentioned the cholinergic toxidrome.
Speaker: There's also an anticholinergic, right, which, I mean, would be a little bit different.
Speaker: Correct.
Speaker: And then, of course, there's a set of hypnotics and opioid, one narcotic or set of hypnotics in which virtually everything is depressed.
Speaker: The heart rate is depressed.
Speaker: The respiratory rate is depressed.
Speaker: The temperature is oftentimes.
Speaker: hypothermic, the pupil size is low, bowel sounds are depressed, and the patients have pretty much dry skin, in a sense.
Speaker: Then you have sympathomimetic, or stimulants, where everything is elevated, such as a heart rate, respiratory rate, temperature, pupil size, bowel sounds are increased, and the patients are often diaphoretic.
Speaker: So these are some of the other types of taxiderms,
Speaker: One doesn't really need any blood levels or urine levels to understand if you have these instances in a clinical scenario of an overdose, these could be quite helpful.
Speaker: And two of the, I guess, situations that are not very common that really don't almost fall into any of those toxidromes and are very specific that I've seen occasionally over the years, but it's something that we read more about than actually see in the critical care, are the serotonin syndrome and the neuromoleptic syndrome.
Speaker: Can you comment a little bit on that?
Speaker: Well, serotonin syndrome, by definition, one has to have change in dose.
Speaker: of an SSRI or similar sort of substance within 48 hours of presentation.
Speaker: And usually the serotonin syndrome, about 70% of the time, resolves within one day.
Speaker: So it's almost unheard of that a serotonin syndrome is lasting for a week or so in this way.
Speaker: It usually resolves within one day, as opposed to neuroleptic malignant syndrome, which the temperatures are extremely high.
Speaker: The patient is rigid, essentially, and unlike serotonin syndrome, where there's quite a bit of tremors, here the patient is very rigid, and it can last for several days or even weeks.
Speaker: So as we evaluate a patient, the first step would be obviously get the history, start with the exam, trying to identify these toxidromes, which, like you said, are going to be very useful in single drug ingestions or single drug toxic effects.
Speaker: The next step, I guess, is starting to get some diagnostic tools.
Speaker: And what are some of the laboratory tests that you would order on a regular basis in somebody who you're suspecting a toxic ingestion?
Speaker: Well, I order the usual test for the most part, and that tells us quite a bit.
Speaker: For example, we order the CMP or complete metabolic profile, looking at the liver function test, the electrolytes, trying to see if there's an anion gap acidosis.
Speaker: But more importantly than that,
Speaker: is to look for the trend is a bicarb going down usually with bad toxic alcohol ingestions or salicylate ingestions that can cause an anion gap acidosis the bicarb and will decrease as the anion gap increases no matter what you do short of dialysis in this way if if a person is getting intravenous fluids and some intravenous bicarbonate sodium bicarbonate and the
Speaker: bicarb is going straight up, in other words, the N9 gap acidosis is normalizing, then it's unlikely to be a significant toxic ingestion because true toxic ingestions that cause a metabolic acidosis, this acidosis is just generated and just continues on unless definitive therapeutic modalities are performed, such as dialysis.
Speaker: So to me, it's not only getting the lab test, but it's also looking at the trends.
Speaker: I oftentimes get osmolality, serum osmolality, to look for an osmogap to consider if it's a toxic alcohol per se.
Speaker: CBC, EKG, particularly focusing on the interval, such as QRS interval and QTC interval.
Speaker: Overall, the SSRIs are known to cause a prolonged QTC over 500 milliseconds.
Speaker: And then oftentimes we do the drug screen, but the drug screen pretty much
Speaker: more or less confirms what we already know in the sense it just gives us a quantitative number as far as the blood tests go as far as salicylate or acetaminophen of course there's no quantitation on the urine drug screen and so those are some of the basic things that I get for just about anyone that comes in with altered mental status
Speaker: So let's dive a little bit more into some of these, I think, that are very important.
Speaker: So the first, I think, take-home message, Jerry, is that you really get like a basic panel of labs, nothing very fancy or specialized, and that you're more interested in following trends and seeing how things are evolving.
Speaker: But you did mention the urine drug screen.
Speaker: And could you just maybe give us some insight into some of the situations where we may have a false positive or a false negative and when it might not be as useful, like you said, in confirming what we're suspecting?
Speaker: Well, there are many false positives with opiates and amphetamines.
Speaker: Almost any over-the-counter cold pill or pill used for colds can cause a positive amphetamine.
Speaker: And opioids are really for codeine and morphine.
Speaker: Synthetic opioids can give you a positive opiate drug screen, but so can poppy seeds.
Speaker: And so the drug screens in itself have some utility, but relatively limited utility.
Speaker: The one thing I always say is that if a person comes in with a positive barbiturate screen, that has to be investigated because I've seen too many instances where a person comes into the hospital with a positive barbiturate screen and they're not given barbiturates and they may be surreptitiously taking a medication that has barbiturates and they go into barbiturate withdrawal.
Speaker: in the hospital and barbitral withdrawal is probably the most lethal type of drug withdrawal there is and So that's one thing on a drug screen that should never be ignored When it comes to cannabinoids or marijuana There is roughly a four percent or five percent false positive rate turns out omeprazole Can cause a false positive marijuana screen
Speaker: And so there are several types of drugs that can cause false positive.
Speaker: That's why it's important in the critical care situation, we always get the confirmation.
Speaker: The immunoassay is the drug screen, gas chromatography and mass spectromody or GC mass spec is the confirmation.
Speaker: And so I would always suggest to get a confirmation test done
Speaker: on the drug screen for patients in the intensive care unit.
Speaker: So we know precisely what was taken and we know precisely how much was taken.
Speaker: And that can be determined from a urinary amount of certain drugs.
Speaker: So I think that's an important lesson.
Speaker: And also I think, like you mentioned earlier, always correlating what you're seeing clinically, right?
Speaker: So if you have a positive amphetamine in your urine drug screen, but somebody is depressed, not breathing with a non-reactive pupil, maybe it's not amphetamine that's a false positive.
Speaker: So I think kind of like making sure that you correlate with what you're seeing at the bedside.
Speaker: Correct.
Speaker: Usually the drug screens, one can predict what the drug screens can show.
Speaker: And as I said,
Speaker: To me, the purpose of all these tests is to confirm your clinical suspicion, not to make a diagnosis, but to confirm it.
Speaker: So you also mentioned gaps, and obviously I think that everybody's very familiar with the anion gap and the acronyms that we all learned in med school with mud piles and some of the causes of increased anion gap acidosis, which a lot of them are toxic ingestions or toxin substances.
Speaker: What about the osmoneur gap?
Speaker: Can you tell us a little bit more about that?
Speaker: Do you routinely check that?
Speaker: Sure.
Speaker: I check it in increasing acidosis.
Speaker: If an individual has a bicarb that's going down or anion gap that's going up, I will routinely check that.
Speaker: And sermosmols are highest for methanol, but can occur with ethylene glycol and isopropyl alcohol.
Speaker: However, isopropyl alcohol does not give you an anion gap acidosis.
Speaker: So that's one difference there.
Speaker: Other drugs, such as high Depakote levels, can, in theory, give you a little bit of an osmolar gap.
Speaker: Depakote is essentially an alcohol in this way.
Speaker: But the two most commons are ethylene glycol and methanol, and methanol has a highest contribution to the osmolar gap, so exceedingly high serum osmols, around 400 or so, is usually methanol.
Speaker: Okay, so obviously, not only important for boards, but also important when we're taking care of patients and making sure that we're looking into this to get some clues into what have happened, especially somebody who might be unresponsive and unable to provide a good history.
Speaker: Yes.
Speaker: What about, Jerry, what about the oxygen saturation gap?
Speaker: I mean, is that something that you only do in certain cases?
Speaker: How do you think about that?
Speaker: That's I only do that I very rarely do it because usually we can get carbon monoxide levels and things like that pretty rapidly and especially with the pulse ox Ametree type of technology that can do screenings for that and I'd like to get actual methanol levels.
Speaker: I'm sorry my hemoglobin levels Along with cyanide levels as necessary, but the site with cyanide
Speaker: which really is not a big factor in the oxygen saturation gap, you can usually tell that with no change in the venous O2 and the arterial O2 concentrations.
Speaker: So there are other ways to measure that.
Speaker: We don't use that as much, although that is a kind of a question the board's like.
Speaker: Yeah.
Speaker: what about a you mentioned some throughout the conversation but could you just give us maybe a short list of medic a of substances or medications or K toxins where a specific level is readily available and might be useful well available available levels are usually present for salicylates acetaminophen and ethyl alcohol so
Speaker: Those are three things that can be done usually in the hospital setting.
Speaker: And actually, on individuals who have a psychiatric history and they're coming in with an unknown ingestion or altered mental status, I almost always will get a carbonazepine level, valproc acid level, and lithium level.
Speaker: Those, again, can be done right away, usually within the hospital.
Speaker: And the whole point is a diagnosis can be made with just getting those levels because these individuals can have all sorts of variable types of neurologic signs that can make it very difficult to make the diagnosis without the levels.
Speaker: And especially since a lot of these patients who may have a psychiatric history may not be able to give you a history of what medications they are or that may not be easily obtainable.
Speaker: So those levels I often will get.
Speaker: If I have an unknown acidosis, I also will get an iron level, a serum iron level, because that can be a cause for an acidosis.
Speaker: So I think that a lot of these, like you mentioned, are going to be readily available in more obscure toxic congestions.
Speaker: Obviously, having an ongoing conversation with our poison center and sending some labs to a referral center might be what we need, but these are very, very, very valuable.
Speaker: Is there any value in digoxin levels?
Speaker: We don't see as much digoxin, but people still take it.
Speaker: If a person has a crazy, if I can use that term, cardiac rhythm, a very abnormal one, bidirectional ventricular tachycardia, for example, or something along those lines, an elevated potassium with elevated renal function test or acute renal failure,
Speaker: and there's an unknown ingestion, that might be helpful.
Speaker: That might be the place to get these digoxin levels.
Speaker: Also, certain plants, such as foxglove, can have measurable dig levels on ingestion, especially in children.
Speaker: Excellent.
Speaker: So I guess that as we work on the diagnosis, a lot of times these patients, especially when they arrive to the hospital, and the ones that we're going to be seeing are going to be critically ill.
Speaker: The old teaching was you start with a coma cocktail,
Speaker: Can you maybe start telling us what are the first interventions that you start doing in terms of therapy and what is the current thoughts of a coma cocktail?
Speaker: What are the things that we should be doing up front?
Speaker: Certainly.
Speaker: First, we always do the ABCs, airway breathing circulation aspect.
Speaker: The coma cocktail is usually done by EMTs or the paramedics as far as giving oxygen, making sure the glucose is appropriate.
Speaker: Diamonds prevent Wernicke-Kaushikov's syndrome when giving the glucose and naloxone.
Speaker: Naloxone was given over 26,000 times according to poison centers in the year 2017.
Speaker: So that is one of the more common antidotes they're given.
Speaker: It is of interest, Sergio, that only about 5% of all overdoses requires an antidote, which means that 95%
Speaker: overdoses called into poison centers don't get an antidote and are for the most part treated successfully with supportive care decontamination and the like in the sense and so that that is one aspect that's probably the most important aspect overall besides decontamination and antidotes is supportive care but naloxone is one of our most successful antidotes it reverses opiate
Speaker: and opioid toxicity rapidly as most individuals know.
Speaker: It can also help reverse clonidine toxicity, certain sedatives like valproic acid.
Speaker: It has been used for benzos, although flamazinol is much better.
Speaker: But it is, as I stated, very successful in increasing the respiratory rate in opioid overdose.
Speaker: Usually the indication is to give it if respiratory rate is under 10.
Speaker: about eight or so.
Speaker: And I had read, I mean, and I think that we're going to talk about specific toxins and toxicities in a future episode, but I think naloxone, like you mentioned, Jerry, because of the amount that is utilized every year and because of within the range of toxic ingestions, probably is by far the most utilized and effective antidote.
Speaker: And I think every listener probably has had a patient that received naloxone.
Speaker: It's something that we see on a regular basis.
Speaker: Could you tell us a little bit more about how to best use it and who?
Speaker: I read that if you have somebody with meiosis, a respiratory rate below 12, and ultrasensorium, it is very, very, very likely that if you give them a dose of naloxone, it would work.
Speaker: Yes, as long as in toxicology, we believe in larger doses in most individuals.
Speaker: I don't usually use start at 0.4.
Speaker: Of course, I see a lot of these patients in the emergency department where we want to get their breathing up above 10 or 12 per minute in a sense.
Speaker: And so we give anywhere from 0.8 to 2 milligrams of naloxone.
Speaker: Now that we are in the synthetic stage of the opioid epidemic, that is that we're seeing a lot of fentanyl overdoses, along with methadone and other types of synthetic opioids, naloxone works for that, but doesn't work at the lower doses.
Speaker: So these individuals may need quite a bit more than two milligrams IV of naloxone to reverse their respiratory depression.
Speaker: So I think this is important because I've also seen that people might give a very low dose, like a 0.2 milligram
Speaker: and report that it didn't work.
Speaker: So especially in patients who might have synthetic opioids, that might not be enough.
Speaker: It's not a therapeutic dose.
Speaker: They need a much higher dose, correct?
Speaker: Correct.
Speaker: I believe one should look at doses of 2, 4, 8 milligrams in that ballpark before saying it doesn't work.
Speaker: And what are the dangers of giving an N-Luxone?
Speaker: What should people be aware of?
Speaker: Potential side effects.
Speaker: Obviously withdrawal with some medications would be a concern, but...
Speaker: What should we be careful with?
Speaker: For the most part, that's it.
Speaker: It's a narcotic withdrawal.
Speaker: It doesn't really have any direct cardiac or other types of effects.
Speaker: There's no systemic effects other than the specific mu antagonist, which is the opioid pathway.
Speaker: And so that's pretty much it, is the withdrawal and sometimes the hyperagenergic response that comes with the withdrawal.
Speaker: But that usually resolves in about 20 to 40 minutes after the naloxone dose.
Speaker: And this is just a question that I've always had, and I don't want to dive too deep into that rabbit hole, which is a specific opioid toxicity.
Speaker: But I always debate or wondered, from a cost efficiency standpoint,
Speaker: Is there a difference of having somebody in the unit on a naloxone drip waiting for their opioids to go away versus having somebody who was intubated just wake up and then extubate them?
Speaker: I'm just curious, I mean, if there's any data on that, Jerry.
Speaker: There's no data on that particular question that I know of.
Speaker: Naloxone drips are pretty harmless in itself.
Speaker: It's very difficult, and I'm not going to say impossible, but very difficult to overdose on naloxone per se in this manner.
Speaker: So I don't know of any specific data looking at that instance overall, but it does make sense that if you can prevent intubation, which is what we try to do with Naloxone administration, that's the goal overall.
Speaker: And my suspicion is from what we're talking right now and from my previous clinical experience is that often patients who come to me intubated to the ICU with an opioid overdose probably did not receive an adequate dose of naloxone as a trial.
Speaker: So they get intubated very quickly as a naloxone failure didn't work naloxone.
Speaker: And it might be because people are utilizing the commonly recommended doses of 0.2 to 0.4, which might be too low.
Speaker: Yes, I believe it should be in milligrams.
Speaker: There's one other aspect is that the heroin that we see is often contaminated with other substances and not just fentanyl or other opioid type of substances.
Speaker: In my area, I see heroin that's contaminated with diphenhydramine.
Speaker: I see heroin that's contaminated with certain antidepressants.
Speaker: And so basically,
Speaker: there are other sedatives that are associated with heroin and heroin overdoses, and it's really more of the other types of the illicit substances other than heroin that's causing the major problems.
Speaker: And so from that aspect, we're dealing not with heroin overdoses per se, but heroin plus something else as far as illicit drugs go.
Speaker: And so in those cases,
Speaker: a few milligrams of naloxone won't be enough.
Speaker: I think that's an important point.
Speaker: So what about the concept of GI decontamination?
Speaker: Obviously, the rationale is to try to remove the toxin before it gets absorbed, but there's been a lot of back and forth and not a lot of literature to support some of the practices that we used to have.
Speaker: And I just wonder what is currently recommended and what do we still do for GI decontamination?
Speaker: Well, back in the old days, uh,
Speaker: and that was back in the early 1980s, if I can use that term, Ipecac was used quite a bit.
Speaker: Ipecac syrup, which causes vomiting, and when I say causes vomiting, the vomiting doesn't really stop.
Speaker: And it was used in 15% of all poisoning exposures or overdoses in 1985.
Speaker: Last year, it was only used in.003%.
Speaker: It's really no longer used anymore.
Speaker: because individuals are vomiting and vomiting and then they become essentially comatose and they're still vomiting and then they seize and they're still vomiting and aspiration occurs and you can't stop the vomiting.
Speaker: So Ipecac is no longer used.
Speaker: That should be confined to the medical textbooks and medical history books in this way.
Speaker: As far as other areas of GI decontamination, which was used about almost 50% of the times,
Speaker: in patients according to the poison center data.
Speaker: Gastric lavage was only used about 1,000 cases.
Speaker: We hardly ever use that.
Speaker: And the reason is because the most you can realistically remove is about 30% by gastric lavage, 30% of the ingested substance.
Speaker: And so the whole aspect of putting literally a garden hose
Speaker: down through someone's esophagus, even when they're awake, to remove at most 30% of the substance just doesn't make sense.
Speaker: And so we hardly ever use gastric lavage anymore.
Speaker: Activated charcoal at one gram per kilogram is probably one of the more common decontamination agents that we use.
Speaker: It is the most common.
Speaker: And it was used in almost 37,000 cases in the year 2017.
Speaker: A single dose, it absorbs, adesorbs,
Speaker: Quite a few substances, not good for cyanide or iron or lithium, but outside of most of those, it's really pretty effective.
Speaker: You can remove almost 50 percent if given within one hour, maybe about 30 percent after about three hours time.
Speaker: The most effective way of GI decontamination is whole-ball irrigation.
Speaker: giving polyethylene glycol at one and a half to two liters an hour for five hours or until the rectal affluent is clear.
Speaker: That can remove as much as 67% of ingested substances.
Speaker: It was used in about 1,600 cases in the year 2017, mostly for the extended release products along with lithium and sometimes iron overdoses, of which activated charcoal doesn't really work well for.
Speaker: So from what you're telling me really in terms of if you have a broad group of patients and don't have like very specific information and you're dealing with maybe polysubstance, it seems that one dose of activated charcoal is what most of those patients would get and the other ones are either not utilized anymore or reserved for very specific cases.
Speaker: That's correct.
Speaker: And actually we're not using activated charcoal in children under five years old or five years old or less.
Speaker: for the most part, not too much anymore, because these children usually don't take enough to cause real problems, and there's more of a problem in giving them the activated charcoal, which no one wants to drink.
Speaker: In 1993, 3.7% of the children received activated charcoal.
Speaker: In 2017, it was only 0.6%, in the sense, in fact, only about 1.4% of all toddlers receive any kind of gastric contamination.
Speaker: And the other way of eliminating toxin is with enhanced elimination.
Speaker: And obviously, the most common modality is dialysis.
Speaker: Can you talk a little bit about that in general terms?
Speaker: And then maybe in the next episode, when we talk about specific toxins, we'll go into more details.
Speaker: But just give us an overview.
Speaker: Well, the two modalities that are most used, hemodialysis being one, was used about 2,600 times in the United States in the year 2017, mostly for lithium,
Speaker: salicylates and the toxic alcohols occasionally for some of the barbiturates overall one the pharmacologic considerations for dialysis include a small volume distribution usually less than one liter per kilogram low protein binding usually less than 70 percent low molecular weight usually less than 600 Daltons and water solubility of course and this is oftentimes a board's question is
Speaker: we oftentimes manipulate the urine pH, making it higher or more alkaline for a certain specific substance such as salicylates or phenobarbital.
Speaker: Those are two substances that can be enhanced by ion trapping as far as its elimination goes.
Speaker: So there's enhanced elimination with salicylates and phenobarb when the urine pH is over 7.5.
Speaker: and alkalinizing the urine does help for those two substances.
Speaker: It also helps for other obscure substances like uranium.
Speaker: So with alkalinization of the urine, Jerry, one of the things that I have often seen is people think that that just involves giving bicarb.
Speaker: It probably involves checking the pH and knowing what you're doing as well, right?
Speaker: Right.
Speaker: Checking the urine pH very frequently and checking the electrolytes because giving this amount of bicarbonate can cause a low potassium, which can cause problems in itself.
Speaker: And what are other maybe therapies that can be utilized in the initial phase of support?
Speaker: I know that there's been enthusiasm with hyperinsulinemia at one point.
Speaker: I don't have a lot of experience with that, but also I know in the OR, I've seen people use high lipid emulsions.
Speaker: Are those therapies still recommended?
Speaker: Are there others that fall in that category?
Speaker: Well, the hyperinsulinemia and euglycemia,
Speaker: Often is used for the calcium channel blockers.
Speaker: It does show to increase the cardiac output in those certain situations The lipid rescue resuscitation Is useful for lipid soluble cardio toxic drugs especially useful for the local anesthetics and some of the antidepressants It acts kind of like a sponge so to speak to help decrease the activity of these kind of drugs at 20% lipid emulsion is used and
Speaker: at about 1.5 milliliters per kilogram bolus over a minute, and then another 0.25 milliliters per kilogram per minute for about 30 to 60 minutes overall.
Speaker: So that can be quite effective.
Speaker: And what about the hyperinsulinemia?
Speaker: Is that really just an insulin drip or it's high doses of insulin?
Speaker: High doses of insulin, about one unit per kilogram or so, as much as one unit per kilogram, and monitoring the sugar or the glucose with that.
Speaker: And that can in my experience really serve to increase the cardiac output transiently and over this period of time, especially in calcium channel blocker overdoses.
Speaker: Excellent.
Speaker: So we've talked about this before, and I know from talks that I've seen you present, and you mentioned actually that only 5% of toxic ingestions called to a portion center got an antidote.
Speaker: So the key really is, and this is where the ICU comes to play, is supportive care.
Speaker: So let's talk a little bit about supportive care in the ICU, Jerry, and I would like to start with maybe just some common indications of which patients come to the ICU.
Speaker: Certainly.
Speaker: Certainly.
Speaker: As far as a criteria for poison patients to the ICU or admitting them some of them are pretty obvious respiratory depression pCO2 over 45 intubated patients cardiac arrhythmia especially those with second or third degree AV blocks hypotension Glasgow coma scores less than 12 will May require some intensive care unit evaluation and intervention increasing increasing metabolic acidosis pulmonary edema caused by an
Speaker: any of these drugs, abnormalities in temperature, prolonged QRS over 0.12 seconds or QTC over 500 milliseconds, body packers, body stuffers in this way.
Speaker: Hyperkalemia due to DIG overdose is another one that automatically requires admission to intensive care units.
Speaker: And that's not even talking about the PEAS intensive care unit, of which acute intoxications account for about 5% of PEAS ICU admissions overall.
Speaker: And the most common intervention there are mechanical ventilations, invasive access, and occasionally dialysis.
Speaker: And I think that in terms of at least my experience clinically, I would say that the most common intervention is hemodynamic monitoring and support followed by
Speaker: mechanical ventilation followed by, in a smaller group, hemodialysis.
Speaker: But these are all things that will obviously happen in the ICU.
Speaker: Is there a specific or maybe some specific situations where it might not be apparent on face value of the high risk and an intensivist could be fooled of patients who need to be in an ICU?
Speaker: Well, in terms of pediatric ICUs, certainly any child who ingested an oral hypoglycemic agent
Speaker: Clonidine, carbon monoxide exposures, in the sense, the drug classes with the highest mortality in children, as far as PEDS-ICU, are narcotics, household products, recreational drugs, antidepressants, in the sense.
Speaker: So basically, any child that's exhibiting symptoms two hours post exposure, and when I say symptoms, I mean clinically significant symptoms,
Speaker: over two hours post exposure should be considered for a peds ICU in in the sense I think oral hypoglycemics is one thing that people may have a false sense of security about and Because these patients can have profound hypoglycemia for literally days Yeah, and I think that it's something that it
Speaker: decades ago has been a source of tremendous legal problems for some of our ED colleagues who would release these patients home after some dextrose when these drugs were all new and then they would have a severe hypoglycemia and devastating consequences so something to think about yes that's the whole point in the sense and these these patients often need intensive monitoring
Speaker: Is there any other situation, I mean, that you would be concerned about?
Speaker: I guess, I mean, it depends also when the patient comes, but we'll talk about it in the next episode.
Speaker: But with acetaminophen toxicity, if you see the patient early enough, you might not be able to identify the tremendous problems that lie ahead, right?
Speaker: That's correct.
Speaker: There's very important aspects regarding acetaminophen.
Speaker: which is similar to iron and salicylates where a person may appear to be well for a few hours and then literally as far as their vital signs and electrolytes along with hepatic status become very sick after about 10, 12 hours.
Speaker: And so there are these delayed effects that can occur with enormous ingestions, usually with acetaminophen ingestions over 150 milligrams per kilogram.
Speaker: is considered, and salicylate ingestions also, over 150 milligrams per kilograms can be considered as potentially lethal.
Speaker: Are there any specific aspects of the supportive care that you want to mention on?
Speaker: I mean, I think that at the end of the day, it's just providing good detail-oriented critical care that looks at the patient as a whole, but are there any specific things that you want to mention in terms of supportive care in the ICU?
Speaker: Well, ventilators was used about 22,000 times, 86% of these in adults, according to poison center statistics, and vasopressors were used 7,700 times.
Speaker: There were 13 toxin-induced transplants that were performed in the year 2017.
Speaker: So these are some of the most important parts and aspects of supportive care, but ventilator and vasopressors, I think, are the two biggest aspects that we talked about earlier.
Speaker: So you talked about body stuffers and body packers.
Speaker: I know that this is not necessarily a common place in a lot of ICUs that our colleagues practice, but depending on the area, it might be.
Speaker: Could you just tell us the distinction and why it's important for them to be in the ICU?
Speaker: Yes, body stuffers are individuals who the police are literally knocking on the door and they're trying to get rid of the cocaine or illicit substance any way they can.
Speaker: And the one way they do it is do it orally.
Speaker: In these cases, intestinal obstruction usually is not seen.
Speaker: It's usually the toxicities are usually seen relatively right away because these things aren't packaged.
Speaker: As opposed to the body packers, where these things are packaged very well to some extent as compared to body stuffers.
Speaker: And so leaking of the packages are somewhat less likely, but can occur.
Speaker: Intestinal obstruction can occur.
Speaker: Usually radiological procedures such as a CT scan may be necessary
Speaker: to see what exactly is going on or how many of these packets are and they may not be radio dense.
Speaker: So within the GI tract usually some radiological technique is necessary.
Speaker: Excellent.
Speaker: I think that this would be a good place to stop for episode one, Jerry.
Speaker: I think that we covered a lot of the general approach to
Speaker: And as I said at the intro, we're planning to do a follow-up part two where we're going to dive deeper into some specific toxicities that might be commonly encountered in the ICU.
Speaker: One of the things that we do at our podcast, Jerry, is at the end of the episode, we ask some questions that tap into the general wisdom of our guest, not related to toxicology.
Speaker: Would that be okay?
Speaker: Yes, of course.
Speaker: So the first question or closing question is, is there a book or books that have influenced you the most or that you have gifted most often to others?
Speaker: Well, I have to say, ironically, one of the books that really influenced me, and I've read it two or three times, is the biography of Louis Armstrong, which I felt was one of the true American geniuses, did not actually take any music lessons.
Speaker: or anything like that and literally gave birth to jazz on his own more or less contemporaneously.
Speaker: And I thought that's a sign of a real genius.
Speaker: And so in this way, it was really eye-opening how a person who never took a music lesson, didn't know how to read music early on, and became one of the most important musicians in the 20th century.
Speaker: Well, I think that's a great recommendation and I definitely will put it in the show notes.
Speaker: I'm a big jazz fan and I do think that a lot of people underestimate the importance culturally that jazz has around the world.
Speaker: And what I think of one of the greatest gifts of United States culture to the world has been jazz and Louis Armstrong definitely is one of the grand grand granddaddies of this genre.
Speaker: So I definitely think that that's something that we will put in the show notes.
Speaker: Excellent.
Speaker: Yes, I think just listening to his Hot 7 and Hot 5 recordings of the 1925 to 1928 is really eye-opening.
Speaker: Absolutely.
Speaker: The second question relates to beliefs.
Speaker: And is there something that you believe to be true in medicine or in life that a lot of other people don't believe or most people don't believe?
Speaker: Yes, and I encounter this all the time.
Speaker: People don't think marijuana or cannabis can be toxic or can be lethal.
Speaker: And certainly that violates one of the number one rules in toxicology as articulated in the 16th century by Paracelsus, the Italian alchemist, who said it's a dose that makes a poison.
Speaker: It's not the substance, it's a dose overall.
Speaker: And I encounter too many people in periods and in positions of responsibility such as legislatures,
Speaker: and leaders that think that cannabis is non-toxic, that think that cannabis cannot kill, that there is a cumulative toxicity that can occur.
Speaker: In 2012 and 2013, there were 46 deaths called into Poison Center, in part attributable to cannabis.
Speaker: And so that's one misconception that I believe needs to be corrected.
Speaker: Well, I think that speaking to Paracelsus, I think that water can kill you, right?
Speaker: Yes.
Speaker: If you drink enough water, you will get back from hyponatremia.
Speaker: So absolutely.
Speaker: Yes, any substance.
Speaker: Any substance taken into excess.
Speaker: And the last question is, is there something that you would want every intensivist or advanced provider that listens to our podcast to know?
Speaker: Could be a quote or a fact.
Speaker: Well, it actually goes with what I just said about cannabis.
Speaker: That individuals, especially young individuals,
Speaker: with an unknown delirium, psychosis, or something like that that tests positive for cannabis, they should get levels.
Speaker: And if the urine level is over 100 nanograms per cc, that should be a consideration that cannabis was taken in excess.
Speaker: And so cannabis can cause things like a variable type of situation, such as a hyperaginergic delirium, or it can look like a stroke.
Speaker: in this sense.
Speaker: And so that's what I would want every intensive to look at.
Speaker: There was a quote by Dr. Bach in the Wall Street Journal in January 2019, and I think that quote was great.
Speaker: Essentially, it says, he said that just because a plant has medicine in it doesn't make the plant medicine.
Speaker: And I think that's true overall in the sense.
Speaker: And I think that that's a great place to stop for part one.
Speaker: Jerry, I really enjoyed the conversation and we will have you back to talk about some specific toxins soon.
Speaker: Look forward to it.
Speaker: Thank you very much.
Speaker: Thank you.
Speaker: Thanks again for listening to Critical Matters.
Speaker: Make sure to subscribe to this podcast on iTunes or Google Play.
Speaker: You can also listen at www.soundphysicians.com backslash podcast.
