Transcript
Speaker: Welcome to Critical Matters, a sound podcast covering a broad range of topics related to the practice of intensive care medicine.
Speaker: Sound provides comprehensive critical care programs to hospitals across the country.
Speaker: To learn more about our programs and career opportunities, visit www.soundphysicians.com.
Speaker: And now, your host, Dr. Sergio Zanotti.
Speaker: Sola dosis facit venenum.
Speaker: is a quote by Paracelcius, which in English translates to the dose makes the poison.
Speaker: So we will pick up where we stopped in our last episode.
Speaker: In today's episode of the podcast, we will continue on the topic of toxicology in the ICU.
Speaker: In our previous episode, part one, we covered the general approach to treatment of poisoned patients.
Speaker: In today's episode, part two, we will dive deeper into the management of specific toxins.
Speaker: We can't cover every potential toxin in one episode, so we will make a deliberate choice to focus on four groups of potential toxins, alcohols, analgesics, cardiovascular drugs, and psychotropic drugs.
Speaker: Our guest is again 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, Jr. 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.
Speaker: Jerry, welcome back to Critical Matters.
Speaker: Thank you very much.
Speaker: It's a pleasure to be here.
Speaker: So in the first episode of this two-part series, we covered a lot of the general management and overview of the approach to the poison patients.
Speaker: Today, I wanted to dive a little bit more into some specific toxins that clinicians might encounter in the ICU and talk about the nuances of treating these specific toxins.
Speaker: You had mentioned in our last episode that there is very little in terms of
Speaker: specific antidotes that are used in common practice, and a lot of it is recognizing the toxin and providing the adequate supportive care.
Speaker: But I would like to start maybe with the alcohols and maybe start by asking you, Jerry, what are the most common intoxications or most common toxicities that we see with different alcohols and start diving into each one of these categories?
Speaker: Certainly.
Speaker: Well, the toxic alcohols are considered primarily three of them.
Speaker: ethylene glycol, methyl alcohol or methanol, and isopropyl alcohol.
Speaker: We're not going to consider ethyl alcohol or ethanol in this discussion.
Speaker: Isopropyl alcohol typically does not give you an acidosis, metabolic acidosis, and therefore it does not require any adjunctive therapy for metabolic acidosis.
Speaker: It is converted to acetone,
Speaker: as being converted to acetone it pretty much eliminated it can cause central nervous system depression at very high acetone levels but outside of that there's very little metabolic consequence to it so essentially the toxic alcohols that we will discuss is ethylene glycol and methanol it only takes about one cc per kilogram of these substances to cause toxicity and the toxicity is one of metabolic acidosis of course methanol and
Speaker: The problem is with regarding blindness along with the metabolic acidosis.
Speaker: And with ethylene glycol, it's kidney failure or renal insufficiency due to the production of oxalates, oxalic acid, glycolic acid, and the like.
Speaker: And so those are the major sequelae of ethylene glycol and methanol.
Speaker: So before we talk a little bit more about the treatment, I do have one quick question on isopropyl alcohol.
Speaker: So as you said, suspect it, I guess, when we have a history of somebody using a substance that might have it with the right clinical findings, or when you don't have an increased standard gap metabagastidosis, but you do see an osmolar gap.
Speaker: Is that correct?
Speaker: Yes, you see an osmolar gap with all three.
Speaker: The largest osmolar gap is with methyl alcohol or methanol.
Speaker: Methylglycol and isopropyl alcohol can prove an osmolar gap, but with isopropyl alcohol, there's no metabolic acidosis.
Speaker: And isopropyl alcohol is found, is that rubbing alcohol, Jerry, usually?
Speaker: Yes, it is usually rubbing alcohol in a very concentrated amount.
Speaker: And the usual scenario is we see it in patients who have a history of alcohol abuse and need an alcohol substitute and believe this is one.
Speaker: We also see it in toddlers who may ingest it accidentally.
Speaker: Okay.
Speaker: And what about ethylene glycol and methanol?
Speaker: What's the usual clinical presentation?
Speaker: Where do people find these alcohols in terms of getting intoxicated with them?
Speaker: Well, typically they're in antifreeze as far as ethylene glycol goes.
Speaker: methanol has been found in certain types of gas products for used for recreation such as model cars and also windshield wiper fluids overall and it's used in window washing fluids as the like is it's kind of an anti-free substance so those are the typical situations that one sees the toxic alcohol particularly methanol and ethylene glycol and is one of these a found in bootleg liquors
Speaker: Bootleg liquors typically had methanol.
Speaker: One had to decant the top 10% of bootleg liquors or else they had methanol poisoning.
Speaker: And actually, methanol poisoning was big during the Prohibition era where bootleg liquors were used quite a bit in the sense there were hundreds of cases in the 1920s of methanol poisoning and blindness in New York City alone due to bootleg liquor.
Speaker: So in patients who come with altered mental status, and as we mentioned in episode one, you find an increased osmolar gap, you should start thinking about these as potential toxic intakes.
Speaker: Are there other clinical findings that might be of interest or that might point you in this direction?
Speaker: Well, the metabolic acidosis is usually seen quite pronounced on presentation of these individuals.
Speaker: In the sense now with the effluent glycol Essentially one sees and not intoxication to a certain extent CNS depression and that's true with methanol to nystagmus is often seen with these or ataxia nausea and vomiting are very common with acute ingestions But at with severe and toxicity one can see the increased central nervous system depression and eventually coma hypotonia and
Speaker: hyporeflexia, probably due to the cerebral edema that can result from either methanol or ethylene glycol.
Speaker: And in terms of danger, I mean, obviously, untreated and unrecognized, these can potentially be very, very lethal, but also cause significant permanent damage, correct?
Speaker: Yes, permanent injury to the kidneys for ethylene glycol, and about one-third of the cases, one will develop permanent blindness in terms of methanol.
Speaker: So are there any cases, Jerry, where you might have a normal osmolar gap or anion gap and have a significant toxicity with one of these alcohols?
Speaker: Certainly.
Speaker: Actually, the osmolar gap is seen early as these metabolic byproducts are being metabolized and formed, and they form the acidosis.
Speaker: So the acidosis is probably a little bit later function that is seen.
Speaker: And it's an anion gap acidosis.
Speaker: The serum CO2 usually goes straight down to virtually undetectable after several hours.
Speaker: But that may not be seen after quite a few hours of ingestion.
Speaker: First it's seen the osmogap and then the anion gap acidosis results.
Speaker: And I think this is an important point because we obviously always talk about the calculation of these gaps, but a normal osmolol gap does not rule out a life-threatening intoxication with ethylene glycol or methanol, right?
Speaker: Especially in view of an acidosis, metabolic acidosis, it is increasing because the metabolites may have already been formed and the parent compound may not be present in very large amounts.
Speaker: So once you suspect or maybe identified, and many times clinically you might have the history that somebody took antifreeze.
Speaker: And obviously makes, I mean, your job a lot easier.
Speaker: But once you've suspected that you have an ethylene glycol or methanol intoxication, what's the next step in terms of workout?
Speaker: What would be the next things that you would order, and how would you approach the treatment?
Speaker: Well, I would approach a treatment.
Speaker: I would obtain, in both cases, a metabolic panel.
Speaker: especially calcium for ethylene glycol because hypocalcemia can occur overall.
Speaker: I would try to obtain a serum osmolality.
Speaker: I would try to obtain an ethylene glycol and methanol concentration, but I realize that that may not be accessible very early.
Speaker: Arterial blood gases should be obtained.
Speaker: Urine analysis, especially looking for calcium oxalate crystals for ethylene glycol or hematuria or proteinuria, can be commonly seen.
Speaker: So that would be the primary workup, our laboratory workup, for these substances because these are metabolic poisons.
Speaker: And in terms of getting precise levels, is that something that most hospitals can do and is that a rapid or slow turnaround?
Speaker: It's a pretty slow turnaround.
Speaker: Most hospitals don't have access to ethyl glycol or methanol levels within the hospital.
Speaker: They probably have, they do have access to serum osmolality.
Speaker: And certainly, if your serum osmolality is quite elevated, and that being with normal electrolytes in the 300s, in the upper 300s, or mid-300s, that could be a clue that there is ethylene glycol or methanol involved.
Speaker: And so from that aspect, serum osmolality would be key.
Speaker: Ethylene glycol or methanol levels would be confirmatory.
Speaker: And in terms of approach mental treatment, as you mentioned, I mean, two of the most feared complications would be, I guess, permanent renal failure and blindness with methanol.
Speaker: What are the next steps in terms of treatment of supportive care?
Speaker: I presume hydration is step number one, management of the acidosis.
Speaker: What are other things that we should be thinking as clinicians?
Speaker: Well, we should be looking at the metabolic abnormalities.
Speaker: Obviously obtaining a serum bicarbon administration of sodium bicarbonate at one to two milliequivalents per kilogram initially should be considered.
Speaker: Of course, for miprazole, which prevents formation of the toxic metabolites, should be considered.
Speaker: Essentially, it's administered as 15 milligrams per kilogram loading dose, followed by four bolus doses of 10 milligrams per kilogram every 12 hours.
Speaker: that is FDA approved for both ethylene glycol and methanol.
Speaker: And then dialysis is a definitive treatment for patients poisoned by toxic alcohols as it clears both the parent compound and toxic metabolites from the blood.
Speaker: It can also correct the metabolic acidosis, electrolyte abnormality, while maintaining the fluid balance in this sense.
Speaker: And so those are the primary treatments.
Speaker: There's adjunctive treatments, for example, folates for methanol and thiamine, 100 milligrams intravenously daily for thiamine, for ethylene glycol, along with pyridoxine, about 100 milligrams intravenous daily to allow the adequate stores of the cofactor needed to convert some of the toxic metabolites to non-toxic metabolites.
Speaker: And I think that historically, when Fomepisol was not widely available or in hospitals that did not have Fomepisol, a lot of people talked about ethanol infusions.
Speaker: Is there any role for that today?
Speaker: Or we just, I mean, really focus.
Speaker: Okay, so that's really something of the past that is not really considered to be standard of care at this point.
Speaker: Correct.
Speaker: And yeah, ethanol should...
Speaker: It should be confined to the history books because farmiprazole really does not have much in the way of toxicity associated with it.
Speaker: And is there a role for using, so a lot of times flamepisol might be used early on, and the idea is that if instituted in a time-sensitive manner, it might even prevent the need for dialysis.
Speaker: But there are still patients, obviously, who will develop the renal failure or other indications for dialysis.
Speaker: Is there a role for using flamepisol in patients who are getting dialysis?
Speaker: Yes.
Speaker: They should be used concurrently for miprazole and hemodialysis.
Speaker: essentially.
Speaker: The dose may have to be adjusted for a firmiprazole.
Speaker: For example, it is removed by hemodialysis, so you may need to repeat the dose after each round of dialysis.
Speaker: Okay.
Speaker: I think this is an important point because, I mean, some people might think it's one or the other.
Speaker: And the reality is that, as you mentioned, I mean, they're meant to be concurrent and probably are synergistic, but it might require adjustment of the dosing.
Speaker: So in terms of making it simple for our clinicians, Jerry, anybody who you have a strong suspicion, high osmolar gap, strong suspicion,
Speaker: of either ethylene glycol or methanol toxicity, who clinically has signs of toxicity, should probably get from episol, right?
Speaker: Yes, that should be considered.
Speaker: There should be a low threshold for giving it since there's very little toxicity associated with epiprazole.
Speaker: Certainly, if the serum ethylene glycol concentration is over 20 milligrams per deciliter or metabolic acidosis, or even a history of potentially toxic ingestion, in a sense, that's when this should be considered.
Speaker: And in terms of pulling the trigger for dialysis, can you give us any guidelines, general guidelines of what would be considered amine indications?
Speaker: Well, metabolic acidosis, in a sense, certainly a pH under 7.2.
Speaker: If there's no response to therapy, if there's already some renal insufficiency noted, if your ethylene glycol concentration, for example, is more than 50, 50 milligrams per deciliter, in a sense.
Speaker: If there's vital sign deterioration despite the advent of supportive care, if the electrolyte abnormalities are severe and not responding to conventional therapy, hemodialysis can be considered and may require multiple sessions.
Speaker: And how long would you get the formepisol?
Speaker: Usually about 48 hours.
Speaker: So I think that clearly, I mean, the key here is really in identifying these substances early on and instituting fromepicillin dialysis when needed in a time-sensitive manner.
Speaker: But these are obviously things that would happen in the purview of the intensive care units, since these patients probably would have been admitted at that point to the ICU.
Speaker: So I think it's very important to keep in mind.
Speaker: Now, we didn't mention a propylene glycol, which is not something that is usually found by itself, but any comments on how this can cause toxicity since we're talking about alcohol?
Speaker: Propylene glycol has been essentially a substitute for various ethylene glycols or things like that.
Speaker: It also has been used as a
Speaker: adjunct in certain types of medications and so it's it's basically I'm not going to say it's non-toxic it it has toxicity in itself overall it can there can be some cardiac issues some cardiac arrhythmias for example associated with profiling glycol especially if it's a
Speaker: given at very large doses, or if there's a large ingestion.
Speaker: So there is some degree of cardiac instability associated with it that we have seen.
Speaker: Having said that, there's also some various substances that it can cause, or it can cause some degree of metabolic abnormalities, but one does not really see it as much.
Speaker: With this it's I mean it is now a major ingredient of antifreeze and deicing fluids But it's also found in various cosmetics liquid detergents and the like Overall in general it's far less toxic than ethylene glycol But at very high doses one can get acidotic because it can be metabolized to lactic acid and
Speaker: I see.
Speaker: So really not as frequent.
Speaker: And I think that we didn't obviously talk about it.
Speaker: I think that we have to go to details.
Speaker: But just, I guess, a reminder that probably the biggest cause of death is ethanol and just the consumption of alcohol socially in the terms of not only intoxications, but probably the effects of driving under the influence of
Speaker: which is another healthcare discussion.
Speaker: But for somebody who comes intoxicated with ethanol, other than supportive care, protecting the airway, IV fluids, anything you would recommend?
Speaker: Well, acidosis can occur at very high ethanol levels in a sense.
Speaker: But, of course, a major aspect is a CNS or central nervous system depression.
Speaker: And so from that aspect, ethanol follows a very predictable pharmacokinetics
Speaker: in the sense that the metabolism is about 10 to 30 milligrams per deciliter per hour.
Speaker: So oftentimes, as far as the acute effects go, all one has to do is pretty much ride it out, so to speak, with supportive care.
Speaker: Yes, dialysis does remove ethanol, but very rarely is it required.
Speaker: And probably the risk would outweigh the benefits of just waiting and supporting the patient, right?
Speaker: Correct.
Speaker: putting the catheter in.
Speaker: Perfect.
Speaker: So why don't we move on to our second category of drugs, which is analgesics.
Speaker: And I would like to start with acetaminophen or Tylenol, which I think is an important cause, obviously, of acute liver failure, but is also something I think that we commonly encounter in
Speaker: in our clinical practices is somebody who took a large dose or somebody who we might not even recognize that took a large dose but can cause problems.
Speaker: How does acetaminophen cause toxicity and what you'll be looking for initially, Jerry?
Speaker: Well, similar to ethylene glycol and methanol, acetaminophen causes this toxicity through its metabolite, which is called NAPQI, which damages the liver architecture.
Speaker: And especially with glutathione depletion,
Speaker: liver failure can occur.
Speaker: It usually can occur with severe toxicity, and we're talking in acute ingestions over 150 milligrams per kilogram.
Speaker: At that dose, the metabolic pathways are overwhelmed, and it's metabolized to the reactive metabolite.
Speaker: And it can be detoxified with glutathione substances or base glutathione-based substances, which in the case in the United States is N-acetylcysteine.
Speaker: And in terms of clinical findings, anything that we should worry about?
Speaker: I think one of the things that has struck me when caring for people who have very bad outcomes is that the initial presentation might be very mild, and I think that people who are not aware with a natural history might really underestimate the severity of the situation.
Speaker: Yes, there is a lag time.
Speaker: There are stages where toxicity concerns
Speaker: concern in the first 12 hours patients may appear to be you know relatively well they may have some mild nausea and vomiting that is almost always see seen along with some right upper quadrant tenderness but the severe cases may not show itself until 12 to 20 hours or so after ingestion and so as far as the treatment goes high degree of suspicion
Speaker: has to occur.
Speaker: I have seen several cases of adolescents that were called gastroenteritis that turned out to be acetaminophen poisoning.
Speaker: And so a high degree of suspicion should be done in these kinds of cases.
Speaker: And what is the maybe historical findings in terms of the quantity that should alert you as this could potentially be a problem I should investigate more?
Speaker: Yes, we're concerned with doses of acute doses
Speaker: of 150 milligrams per kilogram of acetaminophen.
Speaker: Probably need in children at least 200 milligrams per kilogram under six years old.
Speaker: But so any doses in that range, if you don't know milligrams per kilogram, anything over seven and a half or 10 grams, acute ingestion should be considered to be toxic.
Speaker: Okay.
Speaker: And can you tell us a little bit about once you suspect a significant ingestion, what will be the next steps in terms of laboratory in getting ready to treat that patient?
Speaker: Well, as far as the laboratory, once you get, obviously, the serum acetaminophen level, liver enzymes, serum electrolytes, along with renal function tests, INR, should also be obtained, along with a complete blood count, particularly looking at the platelet count.
Speaker: overall and the INR is highly important to look at essentially in the other aspect regarding liver function the acetaminophen level is only good as far as predictive for using the nomogram was called the room at Matthew no program if it's an acute one-time ingestion so it is no good for a chronic ingestion however I believe that it is helpful
Speaker: as far as determining the presence of problems or potential problems with chronic exposure.
Speaker: So I would get an acetaminophen level no matter what.
Speaker: And I think that if you know that the ingestion occurred, let's say, within the last four hours, that's the sweet spot for the Ruma-Matthew normogram, correct?
Speaker: Correct.
Speaker: It usually starts at four hours.
Speaker: And then the half-life is four hours in acetaminophen overdose.
Speaker: And so serum levels over 150 milligrams per liter should be thought of as potentially toxic in acute ingestions at four hours.
Speaker: And in terms of, before we get into how you would use the normogram very simply, what would you do in patients who you don't know the time or are chronic ingestors and you suspect toxicity?
Speaker: though that can be quite a bit more problematic.
Speaker: Certainly, if your liver enzymes are elevated, usually SGOT higher than SGPT.
Speaker: So if your liver enzymes are elevated, you show or a patient has symptoms such as nausea, vomiting that may be kind of nebulous after chronic acetaminophen use, those should be suspicious for acetaminophen toxicity and consideration
Speaker: of anacetylcysteine should be given.
Speaker: And in terms of just using the normogram, to make it very simple, it's called the RUMAC Matthew Normogram.
Speaker: I believe it was developed by pediatricians, but it's, I'm sure, widely available in emergency departments and in textbooks and online.
Speaker: And the idea is that if you knew when the ingestion was, you would just plot the hours versus the level you have,
Speaker: And if your level is above the possible hepatic toxicity, it's a green light to go ahead and treat, correct?
Speaker: Correct.
Speaker: It is very useful for acute ingestions.
Speaker: It is not useful for chronic ingestions or not predictive.
Speaker: It's also less useful for the extended release ingestions, so the acetaminophen that's extended release.
Speaker: And I think that the other point that's always something that comes up, I mean, clinically, is that when in doubt, I think the treatment probably benefits outweigh the risk of giving treatment.
Speaker: Is that correct?
Speaker: Yes.
Speaker: I believe that early institution of N-acetylcysteine will be prudent in most cases.
Speaker: In fact, I often use it for virtually any type of chemical-induced acute liver insufficiency.
Speaker: In this way and so we're using an an astylcysteine for quite a few other things that can cause liver such as hepatic ischemia Which is not really chemically induced I've used it for hyperthermia for gold induced for example liver insufficiency and other types of chemical induced liver insufficiency it's been shown to be somewhat effective for some of the herbal products such as germander liver insufficiency so so
Speaker: NS-ylcysteine may be quite useful at the protocol given for acetaminophen overdose for several types of acute liver failure that for the most part is chemically induced or ischemic produced.
Speaker: And I think that's an important point because a lot of times you might not have confirmation, but under the suspicion of another chemical inducing liver toxicity, it definitely, I mean, it can be a tool to be utilized.
Speaker: And I would imagine that, as we discussed earlier, if we called the poison center, they probably would recommend that based on the clinical findings.
Speaker: Can we dive a little bit more into the protocol itself?
Speaker: So historically, obviously, NSD and system was initially given mostly PO and talk about that protocol and what are the pros and cons.
Speaker: And more recently, in the last years, it's available IV, which is usually the preference, I think, for a lot of ICU clinicians.
Speaker: But can we talk about both of those and how you would give them?
Speaker: Sure.
Speaker: Back in the day, so to speak, it was given almost exclusively orally.
Speaker: at 140 milligrams per kilogram loading dose followed by 70 milligrams per kilogram every four hours.
Speaker: The FDA approved protocol was 72 hours, so that's about 17 maintenance doses.
Speaker: However, the problem was that people would be throwing up and it'd be hard to keep it down and giving antiemetics was often not very effective.
Speaker: So the intravenous protocol was developed and FDA approved back around 2004.
Speaker: Overall, it's considered to be 150 milligrams per kilogram infusion over 60 minutes, followed by 50 milligrams per kilogram infusion over four hours, followed by 6.25 milligrams per kilogram per hour infusion overall, or about 100 milligrams per kilogram over a total of 16 hours.
Speaker: And then if the liver enzymes are still going up, we give another 16-hour infusion after that.
Speaker: So basically it is kind of a three-bag protocol, so to speak, and we continue it until the acetaminophen concentration is not detectable, when the hepatic enzymes are improving, and the other prognostic markers such as pH, lactate, INR, and the like are improving.
Speaker: So in terms of the oral, if somebody was still to use it, I think an important point is that if they were to vomit
Speaker: the dose within an hour of administration, you should consider that dose not given and repeat it, right?
Speaker: Correct.
Speaker: We would repeat the dose.
Speaker: I would also consider continuing the bonding switch with the intravenous protocol.
Speaker: Okay.
Speaker: And for the intravenous, what is the danger of the intravenous administration?
Speaker: The danger of the intravenous administration has been allergic reactions associated with it.
Speaker: Anaphylactoid reactions have been associated less than 1% of the time, but it has occurred.
Speaker: Oftentimes one gets a skin rash, bronchospasm, particularly in patients with asthma, may occur.
Speaker: Those are pretty much treated symptomatically.
Speaker: And so from that aspect, it is relatively safe, although adverse effects have occurred.
Speaker: And I think an important point, which I think is to be emphasized, especially in cases that are very severe, you would treat these reactions symptomatically, but you would continue the infusion of N-cysteine, correct?
Speaker: Correct.
Speaker: Except in the anaphylactoid instances, for the most part, the N-cysteine antidote is given.
Speaker: Okay.
Speaker: And in terms of, you mentioned that you usually give the first bag as a loading dose, the 16-hour infusion as a second bag.
Speaker: And at that point, if you are done with undetectable levels and liver enzymes going down, you probably can stop, which would probably be a very mild intoxication case.
Speaker: But if things are still not in the direction you want them, you would give an additional 16-hour infusion, correct?
Speaker: Yes, an additional 16-hour infusion is usually given if the symptoms are not resolving to our satisfaction.
Speaker: And after that second 16-hour infusion, so we're now at 32-plus hours, if you're still heading in the right direction, would you give a third dose?
Speaker: I have done that, yes.
Speaker: I've given doses as much as three or four of these 16-hour infusions after the initial dose.
Speaker: And I think another aspect of treating these toxicities, Jerry, is that this is actually a cause of irreversible acute liver failure.
Speaker: And it is an indication at one point for transplantation.
Speaker: and there are patients who without a transplant might not survive.
Speaker: Do you have any comments for clinicians in hospitals where they don't have liver transplant?
Speaker: At one point you might consider this patient is not moving in the right direction, or what are some of the signs that might tell you I probably should transfer this patient for further evaluation?
Speaker: Certainly.
Speaker: And there have been some various criteria have been used for transfer.
Speaker: What I use for transfer is
Speaker: is that if they're developed in acidosis, renal insufficiency, encephalopathy, hepatic encephalopathy, evidence of liver failure, INR greater than 1.5, those are some considerations regarding the liver enzyme levels.
Speaker: I believe if the liver enzyme levels are over 1,000 and rising overall, that that consideration should be given to send to a liver specialist or transplant center.
Speaker: So an SGOT over a thousand and rising.
Speaker: Oftentimes in these situations, they're doubling within four to eight hours as far as transaminases go.
Speaker: So these are really dramatic, I mean, cases, I mean, in extremes.
Speaker: And I think it's something that people should definitely take into consideration because like you said, when they first present, they might not appear to be as critical, but things can turn very quickly.
Speaker: Yes, I would also add that if they're hypotensive.
Speaker: Is there any other aspects of treatment that you think are worth mentioning before we move on to another substance?
Speaker: Well, hemodialysis has been used in massive ingestions because it does clear out the acetaminophen, but it's not used routinely because acetylcysteine is so effective as an antone, especially when given within 10 hours.
Speaker: So I've given early, really, I mean, that is the way to go, and very rarely would you require dialysis, but it's something that I've never utilized, but I guess, I mean, in very extreme cases, it might be something that is recommended.
Speaker: So if your poison center says, I would consider dialysis, don't think that this is something that has not been described before, correct?
Speaker: Correct.
Speaker: And as I said, NS-stilcysteine has been used for other types of hepatotoxins, such as carbon tetrachloride,
Speaker: hepatotoxic mushrooms, group 1 mushrooms, amanita phylloides, halothane-induced liver problems, peneroyal oil, even iron overdose it has been used for.
Speaker: And I think that's a very valuable pearl, I think, for the audience that not only for acetaminophen liver toxicity, but for many other chemically-induced hepatotoxicities, it is effective and can be utilized.
Speaker: Yes.
Speaker: So the next agent I wanted to talk about or potential toxin is opioids, which obviously in terms of what's going on in healthcare have become a tremendous problem and truly an epidemic of opioid addiction, I think, has increased significantly the number of opioid-induced deaths and opioid-induced intoxications that our clinicians might see.
Speaker: Why don't we start by just giving us a general overview of what's going on with the opioid epidemic?
Speaker: Well, we're sort of in the third stage of the opioid epidemic.
Speaker: That is that we're seeing quite a few street drug contamination of the synthetics involving synthetic opioids, such as fentanyl and its derivatives.
Speaker: And that is accounting for the massive increase in deaths that we are seeing.
Speaker: The first stage was primarily a prescription drug stage overall.
Speaker: The second stage was a street drug, and now we're seeing the synthetic aspect of the street drug.
Speaker: And so what we're seeing is essentially a fentanyl epidemic.
Speaker: And, of course, the treatment has been on paper pretty simple, naloxone, which is the opioid mu antagonist overall.
Speaker: However, one needs very large doses for these to overcome fentanyl,
Speaker: and other types of synthetic opioid intoxications and poisoning, essentially.
Speaker: So one needs doses significantly over 2 milligrams in these individuals.
Speaker: And I think that this is something that we talked about in the previous episode, which I think is worth reiterating, because I often will see people come in with a toxidrome and maybe the history that is very consistent with an opioid overdose, and they will give a very small dose of naloxone, no effect, and they stop.
Speaker: And I think that, as you mentioned, Jerry, there is a higher prevalence today of fentanyl, synthetic fentanyl being part of these intoxications, and these would require much, much higher doses.
Speaker: So could you just reiterate, I mean, how would you would approach in terms of dosing these patients?
Speaker: Yes, I would repeat the doses every few minutes of naloxone.
Speaker: If there is some small degree of response,
Speaker: or even if there's no response, an individual suspected of an opioid overdose.
Speaker: And so I would give, and then literally double the dose, two, four, eight milligrams, and even over 10 or 16 milligrams in that ballpark before I considered it to be a naloxone failure.
Speaker: Oftentimes, these individuals, as I mentioned last time, may take other substances that are contaminated, not only the fentanyl,
Speaker: with what they think is heroin, but other substance I mentioned diphenhydramine.
Speaker: Quetiapine is also something I've seen quite a bit contaminated with our heroin.
Speaker: So all these substances don't respond to naloxone in a very favorable manner.
Speaker: That is at the usual dose of 0.2 to 2 milligrams IV.
Speaker: They may need much higher doses, and some of these substances, such as diphenhydramine and quetiapine, don't really respond to naloxone.
Speaker: And it would seem to me that with the appropriate interventions in a timely manner, most of these patients should not die.
Speaker: But the problem is that they sustain severe hypoxemia before they get to us and go into cardiac arrest and have then severe anoxic brain damage, or they are basically found too late.
Speaker: Is that correct?
Speaker: That's correct.
Speaker: The irony is that it's been shown that patients
Speaker: there have been increased amount of transplant patients that these individuals have donated organs in terms of transplant because of the hypoxic, it's primarily related to the brain damage per se and to less resistant or more resistant organs to hypoxia such as liver and kidney and heart as compared to brain have been transplanted from these individuals.
Speaker: Yeah, and I think that every clinician who's listening to this podcast will probably have a case of a young patient who had an opioid overdose, who made it to the hospital, was maybe resuscitated, intubated, but never woke up and then died because of anoxic brain injury.
Speaker: So clearly, I mean, once you intervene, they're very salvageable.
Speaker: The problem is that a lot of these patients get to us too late.
Speaker: Any other aspects of treatment other than supportive care and understanding that with the increase in synthetic opioids, we need higher doses of naloxone that you would want to comment on, Jerry?
Speaker: Well, basically supportive care is the key to these aspects, that the long-term or the longer toxicity takes, the more other substances or contaminants should be thought of.
Speaker: For example, if it was pure heroin,
Speaker: that would last for maybe a few hours, certainly less than six hours as far as the comatose aspect.
Speaker: But if a patient remains comatose for, you know, days literally, one has to think of other substances that have occurred or as a contaminant with the heroin.
Speaker: And one of the major sequelae is ARDS acute lung injury, which can develop in some proportion of these individuals suffering on acute opioid overdose.
Speaker: And I think the other question I had for you is just any recommendations of the use of a naloxone drip?
Speaker: Usually, my practice is to whatever effective dose I had to use either half to two-thirds of that on an hourly basis.
Speaker: Is that usually what you would recommend?
Speaker: Yes.
Speaker: It's about two-thirds per hour, and this is really maybe necessary if a long-acting opioid is taken, like methadone, for example.
Speaker: duration of effect of naloxone in itself one injection is maybe about an hour hour and a half and so patients who have ingested the long-acting opioids such as methadone may require this naloxone drip and it is as you say about two-thirds of the dose that was effective for the initial reversal given per hour excellent so I think that we can move on to our last
Speaker: drug in this analgesic category which is salicylates which I think is always very interesting from a board perspective because of the interesting acid-base disorders but why don't you tell us I mean Jerry when do you suspect a salicylate intoxication and what would be the next steps in evaluating it well first of all you brought up a interesting aspect regarding the acid basis disorders because
Speaker: salicylates can cause almost any type of acid-base disorder or mixed acid disorder other than a metabolic alkalosis.
Speaker: One has a pure metabolic alkalosis, that's probably the one thing salicylates don't, does not develop from salicylate poisoning.
Speaker: But just about everything else, in a sense, in terms of acid-base,
Speaker: One can initially, the biggest presenting sign of acute salicylate overdose that one can see right away is tinnitus or hard of hearing.
Speaker: If a person is hard of hearing and they may have a little bit of a respiratory alkalosis or maybe have an increased respiratory rate and some GI upset, that could be very serious.
Speaker: That could be a clue to very serious salicylate poisoning.
Speaker: So in almost all the cases of bad salicylate poisoning, hard of hearing is a major presenting sign.
Speaker: And in terms of a workup from a diagnostic standpoint, what are the labs that you would order?
Speaker: Okay, well, I would order the usual labs as far as basic metabolic profile, INR, CBC.
Speaker: Also, one other aspect are liver function tests or renal tests.
Speaker: UA is important to look because one may have to alkalinize the urine to pH of 7.5 or greater.
Speaker: So looking at the urine pH is somewhat important and salicylate.
Speaker: And one should obtain these levels, specifically the basic metabolic profile and the serum salicylate level serially, probably every few hours until the salicylate levels are going down.
Speaker: And in terms of treatment, I think that you mentioned, obviously, always supportive care.
Speaker: So taking care of the airway, breathing, support.
Speaker: These patients can develop, I mean, different toxic cities in the lung.
Speaker: We can have some pulmonary edema.
Speaker: But these patients also are usually volume depleted.
Speaker: So starting with IV fluids is important.
Speaker: When is dialysis part of the picture?
Speaker: Well, first of all, decontamination can be important.
Speaker: If they come in within a few hours, activated charcoal at one gram per kilogram,
Speaker: can help improve the outcome quite a bit.
Speaker: As far as we do alkaline diuresis, urine alkalinization increases the elimination of salicylates.
Speaker: And so trying to get the urine pH to about 7.5 to 8.
Speaker: Hemodialysis does efficiently remove the salicylate and it can improve the acid base and electrolyte disorders in a sense.
Speaker: We give it with high salicylate levels, usually over 80 milligrams per deciliter after an acute ingestion, be over 50 milligrams per deciliter with chronic ingestions.
Speaker: If the acidosis does not really respond very well, if there is a problem with the urine output or renal toxicity, evidence of central nervous system toxicity, such as seizures or coma or confusion, in the sense that if the clinical
Speaker: all the clinical aspects deteriorate with INR, liver insufficiency, renal insufficiency, acute lung injury.
Speaker: If you cannot alkalinize the urine very well due to inability of sodium bicarbonate to be given in a sense.
Speaker: So these are some of the indications for salicylate ingestion and hemodialysis use.
Speaker: And I think that just an important reminder for our listeners is that
Speaker: really these patients can get quite ill, have high morbidity and mortality, and really we shouldn't delay probably instituting dialysis in patients who are getting sicker very quickly and have a low threshold with these indicators that you mentioned to initiate dialysis as soon as possible because it does take care of the levels and can turn around things pretty quickly, correct?
Speaker: Correct, and also have a low threshold for getting a salicylate level overall because it can look like a gastroenteritis,
Speaker: It can also I've seen it look or mimic to a certain extent diabetic ketoacidosis Overall where the it does increase the blood sugar you may not have the ketones But if one gets a salicylate in in that aspect One may see quite a bit of salicylate toxicity in the DKA type of patients
Speaker: Excellent.
Speaker: And I think that as we continue the discussion, I mean, two of the specific levels that you had mentioned in our previous episode that are always useful to obtain when you have a constellation of symptoms that might indicate an intoxication are the acetaminophen and the salicylate, because when elevated, they're very telling of what's going on and can be very helpful in directing management.
Speaker: Getting the salicylate or acetaminophen levels can be key in those patients.
Speaker: Absolutely.
Speaker: So I guess the next big category is the cardiovascular drugs.
Speaker: And again, I think just by the nature of the number of prescriptions that are written every year for beta blockers and calcium channel blockers, these are common causes of toxicity.
Speaker: And I think that there's not one ED or ICU who doesn't deal with these patients on a yearly basis.
Speaker: I guess we could talk about them later.
Speaker: in a big lump together because they're very similar, but there might be some differences.
Speaker: Why don't we just talk about giving us an overview of beta blocker and calcium channel blockers causing serious adverse events from toxicity?
Speaker: Yes, beta blockers are causing bradycardia and hypotension, although other aspects can occur with it.
Speaker: For example, propranolol can cause seizures.
Speaker: It can cause QRS widening.
Speaker: that can result in ventricular dysrhythmias.
Speaker: Hypoglycemia can develop in kids who've taken too much of the beta blocker.
Speaker: So other aspects can occur with it besides the hypotension and bradycardia.
Speaker: Bronchospasm can also develop in some of these individuals.
Speaker: The onset is usually within six hours, especially with beta blockers.
Speaker: overall but calcium channel blockers it's usually within eight hours.
Speaker: So I think that from a clinical perspective what we usually will see is obviously a hypotension bradycardia and it's usually something that we can identify by history taking either the patient was on these medications or took these medications a lot of times they're there they're accidental overdoses other times it might be an intentional overdose but in terms of treatment
Speaker: What are the first interventions that you would institute?
Speaker: And can you give us specific comments about the role and efficacy of atropine?
Speaker: Well, essentially decontamination, if seen within an hour or two, should be considered in both cases, beta blockers and calcium channel blockers.
Speaker: Standard ACLS treatment regarding bradycardia and hypotension is
Speaker: can be considered in in both cases and so that is that's probably one of the major aspects atropine has will have some positive effect particularly for the beta blockers probably more so than for the calcium channel blockers overall but hypotension is treated in the usual way with fluids calcium infusions have been given for the calcium channel blockers usually the response is very transient
Speaker: And so that aspect, you know, can be quite useful, but only as a transient measure.
Speaker: Vasopressors in the traditional manner, epinephrine, vasopressin even, phenylephrine, can occasionally be effective.
Speaker: They usually, patients usually don't respond to the dopamine or norepinephrine.
Speaker: What we've been using, particularly in calcium channel blockers, is high-dose insulin.
Speaker: unit per kilogram of insulin followed by infusion of 0.1 to 1 unit per kilogram per hour titrate to the blood pressure for about 90 to 100 millimeters mercury beta-cardia usually does not respond to that overall also glucagon can be very good for beta blocker and calcium channel blocker overdose initially 3 to 5 milligrams IV over about a minute or two and
Speaker: and you can repeat a dose up to four to 10 milligrams.
Speaker: And so that could be quite effective.
Speaker: And what we talked about last time, particularly with the calcium channel blockers, lipid emulsion has been used successfully in a few clinical settings.
Speaker: where hypotension was refractory.
Speaker: So I think that just to summarize, I think this is valuable.
Speaker: Obviously, we start with fluids.
Speaker: Atropine, I mean, it can be utilized, but it's usually not as effective.
Speaker: And I think that one of the tenants that I have always kept is that my main target is the hypotension, not the bradycardia.
Speaker: And I really try to keep the blood pressure perfusion.
Speaker: If the perfusion pressure is good, the heart rate becomes less relevant.
Speaker: And there is also...
Speaker: a significant amount of vasodilation that's going on and other reasons why the patient is very hypotensive, not only the bradycardia.
Speaker: Use depressors, as you mentioned.
Speaker: And then glucagon, effective for both, but much more effective for beta blockers, correct?
Speaker: Yes.
Speaker: Glucagon is effective for especially in individuals that respond to the fluid therapy.
Speaker: And insulin therapy, is that more effective for calcium gynoblockers?
Speaker: Yes, but it is potentially effective for beta blockers too.
Speaker: So you would use both.
Speaker: And then the lipid emulsion, as you mentioned, also has been utilized in calcium channel blocker toxicities.
Speaker: Can that be utilized also for beta blockers?
Speaker: Yes, it has been used for beta blockers, especially the lipid soluble beta receptor antagonists.
Speaker: And I think that the other interventions that are more heroic but have been utilized are transvenous pacing.
Speaker: Transcutaneous pacing is not usually as effective but can be utilized short term.
Speaker: And even some cases have described patients being put on ECMO for support that are arrested while these drugs are metabolized.
Speaker: But those are usually much more rare.
Speaker: And I think that with the interventions that you mentioned, usually most of these patients can be taken care of in the ICU.
Speaker: Yes, hemodialysis has been used for beta blockers with relatively limited volumes of distribution, such as atenolol, sodolol, and natolol.
Speaker: So that could also be, I think, a potential therapy to keep in mind.
Speaker: And I think that's why it's always important to get as much information as possible, but also to be in an ongoing conversation with our poison center, as we mentioned in the first episode.
Speaker: That's correct.
Speaker: the last cardiovascular drug that I wanted to ask you I think it obviously has a lot of historical relevance but I think it's still something that is utilized and we still might encounter although least frequently is the Jackson toxicity yes we still encounter this quite frequently and as far as the Jackson and the cardioglycosides in general
Speaker: Basically, we still see cardiac glycosides.
Speaker: It's a naturally occurring toxin, so to speak.
Speaker: It's still in certain plants such as foxglove and the like.
Speaker: But the most common reason, the most common toxicities are usually with digoxin.
Speaker: And in terms of recognizing digoxin toxicity, you can get a digoxin level.
Speaker: But you had mentioned to us earlier that there are some arrhythmias that should make you think this is possible digoxin toxicity.
Speaker: Any comments on how the EKG might help you?
Speaker: Yes, bidirectional ventricular tachycardia may be somewhat diagnostic for it.
Speaker: In the sense if the thing about the Jackson is that it can almost cause any kind of arrhythmia per se especially the AV blocks Disrhythmia and so any almost any kind of heart blocks Due to the increased vagal tone and decreased sympathetic tones Can occur so and especially if you have these heart blocks in?
Speaker: association with marked hyperkalemia and
Speaker: That should be a clue that a cardiac glycoside is involved.
Speaker: And in terms of electrolyte management, obviously potassium is going to be a key element for these digoxin toxicities and making sure that the digoxin is within normal is going to be critical, right?
Speaker: Correct.
Speaker: And the only way to remove the potassium is really either through dialysis, which is not often used for this because it does not increase in clearance of digoxin,
Speaker: But as far as the cardiac glycoside poisoning, the Jackson immune FAB fragments or the Jackson immune antibody fragments, which can rapidly reverse the cardiac arrhythmic effect of these glycosides, but it also can reverse the hyperkalemia.
Speaker: And what about Digibind?
Speaker: I have never utilized it.
Speaker: I have had patients who we almost utilize it but have never really pulled the trigger.
Speaker: What are the thoughts?
Speaker: I mean, obviously, there's very dramatic stories of the first time Digibind was utilized.
Speaker: But what are the recommendations today for utilizing that therapy?
Speaker: Well, as mentioned, if you have elevated potassium over 5 millicrylons per liter in acute overdoses,
Speaker: If you have a progressive bradyarrhythmia, if you have a second or third degree heart block, for example, if your hypotension is refractory in a sense, if you have ingestion over 10 milligrams in adults or over four milligrams in a child, or if you have a serum digoxin concentration greater than 10 nanograms per milliliter after six hours of ingestion, if you have a lack of response or a poor response,
Speaker: to other types of conventional ACLS type of therapy, that's where digoxin immune FAB fragments can be considered.
Speaker: Any other comments on the cardiovascular drugs that you want to share with us, Jerry, before we move on to our last category of drugs?
Speaker: Not really.
Speaker: For the most part, they're supportive, supportive care.
Speaker: The local anesthetics can cause a variety of
Speaker: cardiac arrhythmias that can be resistant to traditional ACLS therapy and so that's where the lipid emulsion therapy can be quite useful excellent and finally the last category of drugs that I wanted to touch on was the psychotropic drugs and start with the cyclic antidepressants which have decreased in a number of prescriptions but historically have been I think a high likelihood of causing mortality
Speaker: intoxications in the ICU and I think it's still important to recognize and treat them appropriately.
Speaker: Yes, fortunately we're seeing fewer and fewer of the tricyclic depressant overdoses which used to be one of the major causes of death due to poisonings in the United States especially with suicidal intent.
Speaker: We still see it on occasion overall and its treatment
Speaker: can be quite complicated because there is no specific antidote per se.
Speaker: And one cannot really get blood levels per se of these substances.
Speaker: So one has to deal with diagnosing this either by history, physical exam, which can be limited, or any laboratory testing, which the EKG comes in.
Speaker: And what would be the profile of a patient other than the history that would make you suspect?
Speaker: So I guess when I see altered mental status in somebody young with abnormal EKG, widened QRS and arrhythmias, that's when I start thinking, could this be a toxicity and could tricyclics be involved?
Speaker: Well, most of tricyclics have some anticholinergic properties.
Speaker: So dilated pupils can be seen, drowsiness, difficulty to arouse,
Speaker: Hallucinations, tachycardia is often very commonly seen with, and as far as early onset and eventually progressing to coma and seizures with QRS prolongation and hypotension.
Speaker: So, but oftentimes these patients will demonstrate some anticholinergic effects.
Speaker: So decreased bowel sounds is also may be evident along with respiratory depression.
Speaker: And in terms of evaluation, so you suspect this, like you said, you can't really get a specific level, but clearly getting the usual lab is going to be important.
Speaker: And then an EKG is critical.
Speaker: And can you tell us how you use the EKG to direct your treatment?
Speaker: Certainly.
Speaker: The EKG is critical.
Speaker: QRS prolongation is one of the key signs.
Speaker: for as far as laboratory monitoring a QRS prolongation over 0.10 is suggestive if a person doesn't have a history of a bundle branch block if it's over QRS widening over 0.12 that can be quite quite a diagnostic
Speaker: Oftentimes, there is additionally QTC prolongation over 500 milliseconds.
Speaker: And so if one has QRS prolongation, QTC prolongation, ventricular arrhythmia is a risk.
Speaker: And I think that these patients obviously merit admission to an ICU.
Speaker: And usually the indication traditionally has been to start sodium bicarbonate.
Speaker: But there's a lot of experiments I've seen very elegant done in animals that suggest that maybe it's not so much the bicarbonate, but the sodium concentration that matters, and perhaps hypertonic saline is an alternative.
Speaker: Can you comment on how you would treat these?
Speaker: Well, I do treat with sodium bicarbonate usually and try to attain a serum pH of 7.45 to 7.55.
Speaker: Try not to exceed 7.6 as an alkalinization pH.
Speaker: That can help decrease the QRS prolongation in this sense by blocking more or less the quinidine type effect.
Speaker: Now, you're right regarding hypertonic saline has been used for severe QRS whitening.
Speaker: We're talking over 160 milliseconds.
Speaker: That has not been responsive.
Speaker: But that, as of yet, it's primarily in case reports, and there have not been any case series, to my knowledge, on that aspect.
Speaker: So the mainstay would be just to alkalinize the blood, start the sodium bicarbonate, and monitor the patients aggressively.
Speaker: And if these patients do develop, I mean, ventricular tachycardias, are they more resistant to normal ACLS treatment?
Speaker: Is there anything else that we should be concerned about or doing?
Speaker: Well, that's where the fat emulsion may come in that has been used in a sense.
Speaker: Ventricular arrhythmias can be managed by the serum alkalinization and then antiarrhythmics.
Speaker: Lidocaine is often ineffective, but that can be used.
Speaker: Amiodarone and DC shock can be given, but they may be ineffective.
Speaker: Penetoyne used to be used and can be thought of for dysrhythmias error and responsive to these other measures.
Speaker: Magnesium overdrive pacing can be used for torsades.
Speaker: But lipid emulsion can be considered with refractory dysrhythmias, especially in the view of hypertension.
Speaker: And is there any role for dialysis in these toxicities?
Speaker: No, not really.
Speaker: Dialysis, these individuals or these drugs have very large volume distributions.
Speaker: They may even have high protein binding.
Speaker: And so dialysis doesn't really affect the elimination.
Speaker: So it's mostly supportive care and treating the underlying potential arrhythmias.
Speaker: Correct.
Speaker: Let's talk a little bit about lithium.
Speaker: It's still utilized, I think, in psychiatric treatments.
Speaker: I think what's interesting of lithium, from my perspective, is not only the potential toxicity, but the fact that it can happen in people who are taking chronically lithium, and they can come in with toxicities.
Speaker: There's not only an acute, but also a chronic form.
Speaker: Could you tell us a little bit more about lithium, Jerry, and how do we encounter it today and in our practices?
Speaker: Yes.
Speaker: Well, of course, the major aspect of lithium, a major encounter, is with therapeutic use for bipolar disorder, in a sense.
Speaker: And that is the most common, and it is given chronically.
Speaker: Very rarely do we see an acute lithium overdose in a patient who is not on lithium.
Speaker: In this way, it's also important industrial materials used in batteries and alloys as such But that's very uncommonly seen Overall, I mean it is a naturally occurring metal in this way and so for the most part acute poisoning is usually seen in the terms of the drug lithium carbonate and
Speaker: In a patient that's been taking it chronically and so we see it's usually considered to be acute and chronic congestion and Are there any specific levels that we should be concerned about that might initiate certain therapeutic context?
Speaker: Well, of course electrolytes particularly sodium urine analysis renal function sometimes thyroid function because chronic lithium therapy can cause hypothyroidism and
Speaker: overall, but the major thing to get is a serum lithium level and probably a serial lithium levels to look at the trend.
Speaker: Now, with lithium, what are the major dangers clinically?
Speaker: What are the, other than CNS alteration, what are things that we would worry about in our patients?
Speaker: Well, number one is the cost.
Speaker: For example, if a person has gastroenteritis that can predispose to lithium poisoning due to dehydration,
Speaker: So one looks for GI signs, nausea, vomiting, diarrhea, dehydration.
Speaker: Usually, moderate poisoning, severe poisoning will have some degree of nystagmus and tremors, along with change in mental status.
Speaker: And that's usually seen more with chronic exposures, in a sense.
Speaker: Abnormal temperature imbalance may occur, hyperthermia, in a sense, on EKG QTC prolongation can often be seen.
Speaker: hypoventilation can occur in concomitant with central nervous system depression.
Speaker: And in terms of indications for further more aggressive treatment, lithium does have a very small volume distribution, I understand, and has been treated with dialysis.
Speaker: Could you give us more details on that?
Speaker: Yes, dialysis is one of the definitive treatments because it has a small volume distribution and it is water-soluble.
Speaker: and virtually no protein binding.
Speaker: And so it does increase lithium clearance, decreases the half-life, especially once you consider it if an individual taken quite a bit of lithium in terms of acute upon chronic.
Speaker: In the sense, if the lithium is greater than five millicolins per liter, probably more than four or increasing, it should be considered.
Speaker: And so, and or if there's mental status changes, confusion and the like, one should consider it in the sense, in the presence of a coma or life-threatening dysrhythmias or seizures, maybe even a lithium level slightly below four miller quilombs per liter, one should contact Reno for possible dialysis.
Speaker: And the last category in this psychotropic drug bucket would be the selective serotonin reoptic inhibitors, or SSRIs, which are very prevalent and are the main reason why tricyclic antidepressants are less common today.
Speaker: What are the concerns that you have with SSRIs?
Speaker: I mean, they're very commonly prescribed.
Speaker: We talked a little bit about the serotonin syndrome last time we spoke, but any thoughts for our audience on SSRIs?
Speaker: Yes, as you stated, SSRIs actually are somewhat safer than tricyclics, which have replaced tricyclic depressants.
Speaker: And actually, tricyclics are somewhat safer than the MAO inhibitors, which it replaced back in the 1970s and 1980s.
Speaker: So these SSRIs are basically can cause some cardiac abnormalities, especially with QTC prolongations.
Speaker: PBCs, premature ventricular contractions, can occur.
Speaker: But most of these individuals that take SSRIs will experience only some mild toxicity, some nausea, mild CNS depression, vomiting, shakiness.
Speaker: Some degrees of sinus tachycardia with QTC prolongation can occur.
Speaker: Hyperreflexia can occur.
Speaker: So these are things that can be looked at.
Speaker: Anything in terms of specific therapies or suspicion?
Speaker: I mean, usually these are shorter-lived, and once we stop them and provide supportive care, usually patients do well, correct?
Speaker: Correct.
Speaker: Hemodialysis is usually not effective.
Speaker: The lipid motion therapy has been used for certain extraordinarily high, almost gargantuan ingestions of SSRIs.
Speaker: It has been used for bupropion, for example, and quetiapine overall.
Speaker: But the treatment for the most part is supportive care, benzodiazepines if seizures occur and the like.
Speaker: There's no specific antidote.
Speaker: Well, I think that, Jerry, as I mentioned at the onset of the episode, we could probably dedicate a whole series of podcasts to
Speaker: to more toxins and other treatments, but we chose to deliberately focus on some of the more common drugs that clinicians might encounter.
Speaker: And I wanted to maybe close the podcast at this moment.
Speaker: And we've talked about last time we had some questions for you.
Speaker: Today I have a couple more questions to close with a topic not related to toxicology.
Speaker: Would that be okay?
Speaker: Of course.
Speaker: So last time I asked you about a book, today I wanted to know about your music taste.
Speaker: And it's interesting because you did mention a biography and a genius musician.
Speaker: But if you were in a desert island and could only listen to one album, we're going to go old school here because now it's all digital, right?
Speaker: But let's suppose it's an album.
Speaker: Which one would it be?
Speaker: Well, I mentioned last time that the Hot 5 and Hot 7 with Louis Armstrong are something I listen to all the time.
Speaker: But also...
Speaker: I think one of the best albums out there, and it's actually on CD, is The Beatles on BBC, the British Broadcasting Network.
Speaker: And so they really play all their hits and their music on the old BBC program that they used to have.
Speaker: And there are two parts to it.
Speaker: Each disc has like 25 different songs on it.
Speaker: It's really incredible if I had one thing to bring, that would be it.
Speaker: So I'll put that on the show notes.
Speaker: And I think that it's hard to go wrong with the Beatles or jazz, but I think that the enduring popularity of the Beatles never ceases to impress me.
Speaker: Like my teenage son, I mean, knows the songs, enjoys them, and they've been around for a long time.
Speaker: But there's a reason why people still enjoy them because they're
Speaker: They're very, very special.
Speaker: So I'll definitely put that in the show notes.
Speaker: And I think it's a great selection.
Speaker: So the Beatles on the BBC.
Speaker: My last question relates to failure.
Speaker: And I think that we're always very fearful of failure.
Speaker: And I think don't like to talk about our failures.
Speaker: But at the end of the day, I believe that failure should be embraced since it's probably one of the best teachers in life.
Speaker: And I was interested to know if you could share with us one of your really good failures, one that really taught you something valuable.
Speaker: Well, when I finished my residency, I wanted to do toxicology.
Speaker: And actually, there are only very few toxicology programs back in 1984 that one could do a fellowship in and get boards in.
Speaker: overall and essentially I failed at being admitted into any of those programs overall and at the time there was no program in Chicago so I hooked up with Dr. Dan Hiroshak who was the only medical toxicologist in the state of Illinois and a truly great physician at Cook County Hospital and we started our own toxicology fellowship back in 1984
Speaker: And now, 35 years later, we have over 50 fellows that graduated from our program.
Speaker: So I think that it's very interesting how something that initially might have been kind of a downer and you felt like, I mean, it was a failure, really led to something much more special and much more meaningful for your life.
Speaker: Because not only, I mean, did you get trained, but you have trained, like you said, I mean, a whole host of toxicologists that I'm sure have done a lot of good to a lot of patients around the country.
Speaker: Yes, it's very satisfying.
Speaker: And in fact, my family and I always say that we're glad I didn't get in because I might have moved out of Chicago in this way.
Speaker: Well, everything happens for a reason.
Speaker: And I think it's what we do with things that happen to us that ultimately matters.
Speaker: So I think this is a great place to stop.
Speaker: Jerry, again, thank you so much for your time, not once but twice in the last couple of weeks.
Speaker: I mean, this two-part toxicology series, I think, has tremendous amount of pearls,
Speaker: and very applicable and very useful information for our bedside clinicians.
Speaker: So I look forward to maybe talking about other topics or more toxicology topics with you and the podcast in the future again.
Speaker: And thanks so much for your time.
Speaker: Thank you very much.
Speaker: Anytime, please call.
Speaker: Thank you for listening to Critical Matters, a sound podcast.
Speaker: Make sure to subscribe to Critical Matters on Apple or Google Podcasts and share with your network.
Speaker: Sound's transforming the way critical care is provided in hospitals across the country.
Speaker: To learn more, visit www.soundphysicians.com.
