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Toxicology in the ICU (Part 2)
15 Plays3 years ago
We are taking a short break from recording new episodes this month. I hope you enjoy this previously released episode on Toxicology in the ICU. This is part two of a two part series. Today’s episode will focus on specific toxic ingestions and their management. Our guest is Dr. Jerrold B. Leikin. Dr. Leikin is the Director of Medical Toxicology at North Shore University Health System-OMEGA which includes several hospitals in Illinois. 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.
Additional Resources:
Link to the website for the American Association of Poison Control Centers: https://aapcc.org/
A three part review series published in CHEST on Toxicology in the ICU:
https://www.ncbi.nlm.nih.gov/pubmed/21896525
https://www.ncbi.nlm.nih.gov/pubmed/21972388
https://www.ncbi.nlm.nih.gov/pubmed/22045882
Albums Mentioned in this Episode:
The Beatles Live at the BBC: Dr. Leikin’s recommendation for the one album he would take on a deserted island: https://amzn.to/2vIrX5M
Recommended
Transcript
Introduction to 'Critical Matters' Podcast
00:00:06
Speaker
Welcome to Critical Matters, a sound podcast covering a broad range of topics related to the practice of intensive care medicine.
00:00:14
Speaker
Sound provides comprehensive critical care programs to hospitals across the country.
00:00:19
Speaker
To learn more about our programs and career opportunities, visit www.soundphysicians.com.
00:00:26
Speaker
And now, your host, Dr. Sergio Zanotti.
Paracelsus Quote and Toxicology Theme
00:00:33
Speaker
Sola dosis facit venenum.
00:00:35
Speaker
is a quote by Paracelcius, which in English translates to the dose makes the poison.
00:00:41
Speaker
So we will pick up where we stopped in our last episode.
Toxicology in the ICU: Overview of Toxins
00:00:44
Speaker
In today's episode of the podcast, we will continue on the topic of toxicology in the ICU.
00:00:49
Speaker
In our previous episode, part one, we covered the general approach to treatment of poisoned patients.
00:00:55
Speaker
In today's episode, part two, we will dive deeper into the management of specific toxins.
00:01:00
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.
Guest Introduction: Dr. Gerald Lakin
00:01:13
Speaker
Our guest is again Dr. Gerald Lakin.
00:01:15
Speaker
Dr. Lakin is currently the Director of Medical Toxicology at North Shore University Health System, Omega, which includes several hospitals in Illinois.
00:01:23
Speaker
He is Associate Director of the Toxicon Consortium based at John H. Stronger, Jr. Hospital of Cook County in Chicago.
00:01:30
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.
00:01:41
Speaker
Dr. Lakin has published extensively in the field of toxicology.
00:01:45
Speaker
Jerry, welcome back to Critical Matters.
00:01:48
Speaker
Thank you very much.
00:01:49
Speaker
It's a pleasure to be here.
00:01:50
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.
00:01:59
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.
Toxic Alcohols: Ethylene Glycol and Methanol
00:02:10
Speaker
You had mentioned in our last episode that there is very little in terms of
00:02:15
Speaker
specific antidotes that are used in common practice, and a lot of it is recognizing the toxin and providing the adequate supportive care.
00:02:23
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?
00:02:38
Speaker
Certainly.
00:02:39
Speaker
Well, the toxic alcohols are considered primarily three of them.
00:02:43
Speaker
ethylene glycol, methyl alcohol or methanol, and isopropyl alcohol.
00:02:48
Speaker
We're not going to consider ethyl alcohol or ethanol in this discussion.
00:02:55
Speaker
Isopropyl alcohol typically does not give you an acidosis, metabolic acidosis, and therefore it does not require any adjunctive therapy for metabolic acidosis.
00:03:09
Speaker
It is converted to acetone,
00:03:12
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
00:03:41
Speaker
The problem is with regarding blindness along with the metabolic acidosis.
00:03:47
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.
00:04:02
Speaker
And so those are the major sequelae of ethylene glycol and methanol.
00:04:07
Speaker
So before we talk a little bit more about the treatment, I do have one quick question on isopropyl alcohol.
00:04:15
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.
00:04:27
Speaker
Is that correct?
00:04:29
Speaker
Yes, you see an osmolar gap with all three.
00:04:31
Speaker
The largest osmolar gap is with methyl alcohol or methanol.
00:04:35
Speaker
Methylglycol and isopropyl alcohol can prove an osmolar gap, but with isopropyl alcohol, there's no metabolic acidosis.
00:04:42
Speaker
And isopropyl alcohol is found, is that rubbing alcohol, Jerry, usually?
00:04:46
Speaker
Yes, it is usually rubbing alcohol in a very concentrated amount.
00:04:53
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.
00:05:01
Speaker
We also see it in toddlers who may ingest it accidentally.
00:05:04
Speaker
Okay.
00:05:05
Speaker
And what about ethylene glycol and methanol?
00:05:08
Speaker
What's the usual clinical presentation?
00:05:09
Speaker
Where do people find these alcohols in terms of getting intoxicated with them?
00:05:15
Speaker
Well, typically they're in antifreeze as far as ethylene glycol goes.
00:05:20
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
00:05:50
Speaker
Bootleg liquors typically had methanol.
00:05:53
Speaker
One had to decant the top 10% of bootleg liquors or else they had methanol poisoning.
00:06:00
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.
00:06:17
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.
00:06:31
Speaker
Are there other clinical findings that might be of interest or that might point you in this direction?
00:06:38
Speaker
Well, the metabolic acidosis is usually seen quite pronounced on presentation of these individuals.
00:06:47
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
00:07:15
Speaker
hyporeflexia, probably due to the cerebral edema that can result from either methanol or ethylene glycol.
00:07:23
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?
00:07:36
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.
00:07:46
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?
00:07:56
Speaker
Certainly.
00:07:57
Speaker
Actually, the osmolar gap is seen early as these metabolic byproducts are being metabolized and formed, and they form the acidosis.
00:08:10
Speaker
So the acidosis is probably a little bit later function that is seen.
00:08:15
Speaker
And it's an anion gap acidosis.
00:08:18
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The serum CO2 usually goes straight down to virtually undetectable after several hours.
00:08:24
Speaker
But that may not be seen after quite a few hours of ingestion.
00:08:29
Speaker
First it's seen the osmogap and then the anion gap acidosis results.
00:08:34
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?
00:08:49
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.
00:09:01
Speaker
So once you suspect or maybe identified, and many times clinically you might have the history that somebody took antifreeze.
00:09:09
Speaker
And obviously makes, I mean, your job a lot easier.
00:09:12
Speaker
But once you've suspected that you have an ethylene glycol or methanol intoxication, what's the next step in terms of workout?
00:09:20
Speaker
What would be the next things that you would order, and how would you approach the treatment?
00:09:25
Speaker
Well, I would approach a treatment.
00:09:27
Speaker
I would obtain, in both cases, a metabolic panel.
00:09:30
Speaker
especially calcium for ethylene glycol because hypocalcemia can occur overall.
00:09:37
Speaker
I would try to obtain a serum osmolality.
00:09:41
Speaker
I would try to obtain an ethylene glycol and methanol concentration, but I realize that that may not be accessible very early.
00:09:47
Speaker
Arterial blood gases should be obtained.
00:09:51
Speaker
Urine analysis, especially looking for calcium oxalate crystals for ethylene glycol or hematuria or proteinuria, can be commonly seen.
00:10:00
Speaker
So that would be the primary workup, our laboratory workup, for these substances because these are metabolic poisons.
00:10:09
Speaker
And in terms of getting precise levels, is that something that most hospitals can do and is that a rapid or slow turnaround?
00:10:16
Speaker
It's a pretty slow turnaround.
00:10:17
Speaker
Most hospitals don't have access to ethyl glycol or methanol levels within the hospital.
00:10:24
Speaker
They probably have, they do have access to serum osmolality.
00:10:28
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.
00:10:45
Speaker
And so from that aspect, serum osmolality would be key.
00:10:49
Speaker
Ethylene glycol or methanol levels would be confirmatory.
00:10:53
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
Treatment for Toxic Alcohol Poisoning
00:11:03
Speaker
methanol.
00:11:03
Speaker
What are the next steps in terms of treatment of supportive care?
00:11:07
Speaker
I presume hydration is step number one, management of the acidosis.
00:11:12
Speaker
What are other things that we should be thinking as clinicians?
00:11:15
Speaker
Well, we should be looking at the metabolic abnormalities.
00:11:19
Speaker
Obviously obtaining a serum bicarbon administration of sodium bicarbonate at one to two milliequivalents per kilogram initially should be considered.
00:11:30
Speaker
Of course, for miprazole, which prevents formation of the toxic metabolites, should be considered.
00:11:40
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.
00:11:49
Speaker
that is FDA approved for both ethylene glycol and methanol.
00:11:55
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.
00:12:06
Speaker
It can also correct the metabolic acidosis, electrolyte abnormality, while maintaining the fluid balance in this sense.
00:12:14
Speaker
And so those are the primary treatments.
00:12:17
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.
00:12:40
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.
00:12:51
Speaker
Is there any role for that today?
00:12:53
Speaker
Or we just, I mean, really focus.
00:12:55
Speaker
Okay, so that's really something of the past that is not really considered to be standard of care at this point.
00:13:01
Speaker
Correct.
00:13:02
Speaker
And yeah, ethanol should...
00:13:04
Speaker
It should be confined to the history books because farmiprazole really does not have much in the way of toxicity associated with it.
00:13:14
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.
00:13:26
Speaker
But there are still patients, obviously, who will develop the renal failure or other indications for dialysis.
00:13:32
Speaker
Is there a role for using flamepisol in patients who are getting dialysis?
00:13:36
Speaker
Yes.
00:13:38
Speaker
They should be used concurrently for miprazole and hemodialysis.
00:13:43
Speaker
essentially.
00:13:44
Speaker
The dose may have to be adjusted for a firmiprazole.
00:13:51
Speaker
For example, it is removed by hemodialysis, so you may need to repeat the dose after each round of dialysis.
00:13:59
Speaker
Okay.
00:14:00
Speaker
I think this is an important point because, I mean, some people might think it's one or the other.
00:14:04
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.
00:14:12
Speaker
So in terms of making it simple for our clinicians, Jerry, anybody who you have a strong suspicion, high osmolar gap, strong suspicion,
00:14:23
Speaker
of either ethylene glycol or methanol toxicity, who clinically has signs of toxicity, should probably get from episol, right?
00:14:32
Speaker
Yes, that should be considered.
00:14:33
Speaker
There should be a low threshold for giving it since there's very little toxicity associated with epiprazole.
00:14:39
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.
00:14:53
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?
00:15:01
Speaker
Well, metabolic acidosis, in a sense, certainly a pH under 7.2.
00:15:07
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.
00:15:21
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.
00:15:39
Speaker
And how long would you get the formepisol?
00:15:43
Speaker
Usually about 48 hours.
00:15:46
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.
00:15:57
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.
00:16:05
Speaker
So I think it's very important to keep in mind.
00:16:08
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?
00:16:22
Speaker
Propylene glycol has been essentially a substitute for various ethylene glycols or things like that.
00:16:33
Speaker
It also has been used as a
00:16:37
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
00:17:06
Speaker
given at very large doses, or if there's a large ingestion.
00:17:11
Speaker
So there is some degree of cardiac instability associated with it that we have seen.
00:17:20
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.
00:17:37
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
00:18:01
Speaker
I see.
00:18:01
Speaker
So really not as frequent.
00:18:03
Speaker
And I think that we didn't obviously talk about it.
00:18:06
Speaker
I think that we have to go to details.
00:18:07
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
00:18:23
Speaker
which is another healthcare discussion.
00:18:26
Speaker
But for somebody who comes intoxicated with ethanol, other than supportive care, protecting the airway, IV fluids, anything you would recommend?
00:18:35
Speaker
Well, acidosis can occur at very high ethanol levels in a sense.
00:18:41
Speaker
But, of course, a major aspect is a CNS or central nervous system depression.
00:18:47
Speaker
And so from that aspect, ethanol follows a very predictable pharmacokinetics
00:18:53
Speaker
in the sense that the metabolism is about 10 to 30 milligrams per deciliter per hour.
00:19:00
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.
00:19:10
Speaker
Yes, dialysis does remove ethanol, but very rarely is it required.
00:19:16
Speaker
And probably the risk would outweigh the benefits of just waiting and supporting the patient, right?
00:19:20
Speaker
Correct.
00:19:22
Speaker
putting the catheter in.
00:19:24
Speaker
Perfect.
Acetaminophen Toxicity and Treatment
00:19:25
Speaker
So why don't we move on to our second category of drugs, which is analgesics.
00:19:29
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
00:19:40
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.
00:19:50
Speaker
How does acetaminophen cause toxicity and what you'll be looking for initially, Jerry?
00:19:56
Speaker
Well, similar to ethylene glycol and methanol, acetaminophen causes this toxicity through its metabolite, which is called NAPQI, which damages the liver architecture.
00:20:06
Speaker
And especially with glutathione depletion,
00:20:10
Speaker
liver failure can occur.
00:20:11
Speaker
It usually can occur with severe toxicity, and we're talking in acute ingestions over 150 milligrams per kilogram.
00:20:20
Speaker
At that dose, the metabolic pathways are overwhelmed, and it's metabolized to the reactive metabolite.
00:20:27
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.
00:20:39
Speaker
And in terms of clinical findings, anything that we should worry about?
00:20:45
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.
00:21:02
Speaker
Yes, there is a lag time.
00:21:04
Speaker
There are stages where toxicity concerns
00:21:08
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
00:21:35
Speaker
has to occur.
00:21:36
Speaker
I have seen several cases of adolescents that were called gastroenteritis that turned out to be acetaminophen poisoning.
00:21:43
Speaker
And so a high degree of suspicion should be done in these kinds of cases.
00:21:49
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?
00:21:59
Speaker
Yes, we're concerned with doses of acute doses
00:22:04
Speaker
of 150 milligrams per kilogram of acetaminophen.
00:22:08
Speaker
Probably need in children at least 200 milligrams per kilogram under six years old.
00:22:15
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.
00:22:29
Speaker
Okay.
00:22:30
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?
00:22:39
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.
00:23:00
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
00:23:26
Speaker
as far as determining the presence of problems or potential problems with chronic exposure.
00:23:36
Speaker
So I would get an acetaminophen level no matter what.
00:23:40
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?
00:23:50
Speaker
Correct.
00:23:51
Speaker
It usually starts at four hours.
00:23:53
Speaker
And then the half-life is four hours in acetaminophen overdose.
00:23:59
Speaker
And so serum levels over 150 milligrams per liter should be thought of as potentially toxic in acute ingestions at four hours.
00:24:07
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?
00:24:21
Speaker
though that can be quite a bit more problematic.
00:24:25
Speaker
Certainly, if your liver enzymes are elevated, usually SGOT higher than SGPT.
00:24:33
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
00:24:51
Speaker
of anacetylcysteine should be given.
00:24:55
Speaker
And in terms of just using the normogram, to make it very simple, it's called the RUMAC Matthew Normogram.
00:25:04
Speaker
I believe it was developed by pediatricians, but it's, I'm sure, widely available in emergency departments and in textbooks and online.
00:25:13
Speaker
And the idea is that if you knew when the ingestion was, you would just plot the hours versus the level you have,
00:25:21
Speaker
And if your level is above the possible hepatic toxicity, it's a green light to go ahead and treat, correct?
00:25:30
Speaker
Correct.
00:25:31
Speaker
It is very useful for acute ingestions.
00:25:33
Speaker
It is not useful for chronic ingestions or not predictive.
00:25:36
Speaker
It's also less useful for the extended release ingestions, so the acetaminophen that's extended release.
00:25:46
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.
00:25:55
Speaker
Is that correct?
00:25:57
Speaker
Yes.
00:25:58
Speaker
I believe that early institution of N-acetylcysteine will be prudent in most cases.
00:26:04
Speaker
In fact, I often use it for virtually any type of chemical-induced acute liver insufficiency.
00:26:12
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
00:26:41
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.
00:26:52
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.
00:27:04
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.
00:27:14
Speaker
Can we dive a little bit more into the protocol itself?
00:27:16
Speaker
So historically, obviously, NSD and system was initially given mostly PO and talk about that protocol and what are the pros and cons.
00:27:23
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.
00:27:31
Speaker
But can we talk about both of those and how you would give them?
00:27:35
Speaker
Sure.
00:27:36
Speaker
Back in the day, so to speak, it was given almost exclusively orally.
00:27:40
Speaker
at 140 milligrams per kilogram loading dose followed by 70 milligrams per kilogram every four hours.
00:27:46
Speaker
The FDA approved protocol was 72 hours, so that's about 17 maintenance doses.
00:27:51
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.
00:28:00
Speaker
So the intravenous protocol was developed and FDA approved back around 2004.
00:28:07
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.
00:28:30
Speaker
And then if the liver enzymes are still going up, we give another 16-hour infusion after that.
00:28:37
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.
00:28:58
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
00:29:06
Speaker
the dose within an hour of administration, you should consider that dose not given and repeat it, right?
00:29:15
Speaker
Correct.
00:29:15
Speaker
We would repeat the dose.
00:29:17
Speaker
I would also consider continuing the bonding switch with the intravenous protocol.
00:29:21
Speaker
Okay.
00:29:21
Speaker
And for the intravenous, what is the danger of the intravenous administration?
00:29:27
Speaker
The danger of the intravenous administration has been allergic reactions associated with it.
00:29:32
Speaker
Anaphylactoid reactions have been associated less than 1% of the time, but it has occurred.
00:29:38
Speaker
Oftentimes one gets a skin rash, bronchospasm, particularly in patients with asthma, may occur.
00:29:43
Speaker
Those are pretty much treated symptomatically.
00:29:47
Speaker
And so from that aspect, it is relatively safe, although adverse effects have occurred.
00:29:56
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?
00:30:09
Speaker
Correct.
00:30:10
Speaker
Except in the anaphylactoid instances, for the most part, the N-cysteine antidote is given.
00:30:17
Speaker
Okay.
00:30:19
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.
00:30:26
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.
00:30:40
Speaker
But if things are still not in the direction you want them, you would give an additional 16-hour infusion, correct?
00:30:46
Speaker
Yes, an additional 16-hour infusion is usually given if the symptoms are not resolving to our satisfaction.
00:30:53
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?
00:31:02
Speaker
I have done that, yes.
00:31:04
Speaker
I've given doses as much as three or four of these 16-hour infusions after the initial dose.
00:31:13
Speaker
And I think another aspect of treating these toxicities, Jerry, is that this is actually a cause of irreversible acute liver failure.
00:31:22
Speaker
And it is an indication at one point for transplantation.
00:31:26
Speaker
and there are patients who without a transplant might not survive.
00:31:31
Speaker
Do you have any comments for clinicians in hospitals where they don't have liver transplant?
00:31:37
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?
00:31:47
Speaker
Certainly.
00:31:48
Speaker
And there have been some various criteria have been used for transfer.
00:31:53
Speaker
What I use for transfer is
00:31:55
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.
00:32:11
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.
00:32:24
Speaker
So an SGOT over a thousand and rising.
00:32:27
Speaker
Oftentimes in these situations, they're doubling within four to eight hours as far as transaminases go.
00:32:35
Speaker
So these are really dramatic, I mean, cases, I mean, in extremes.
00:32:37
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.
00:32:49
Speaker
Yes, I would also add that if they're hypotensive.
00:32:52
Speaker
Is there any other aspects of treatment that you think are worth mentioning before we move on to another substance?
00:32:58
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.
00:33:12
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.
00:33:23
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?
00:33:30
Speaker
Correct.
00:33:31
Speaker
And as I said, NS-stilcysteine has been used for other types of hepatotoxins, such as carbon tetrachloride,
00:33:39
Speaker
hepatotoxic mushrooms, group 1 mushrooms, amanita phylloides, halothane-induced liver problems, peneroyal oil, even iron overdose it has been used for.
00:33:51
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.
00:34:04
Speaker
Yes.
00:34:05
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.
Opioid Epidemic and Overdose Treatment
00:34:26
Speaker
Why don't we start by just giving us a general overview of what's going on with the opioid epidemic?
00:34:34
Speaker
Well, we're sort of in the third stage of the opioid epidemic.
00:34:37
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.
00:34:50
Speaker
And that is accounting for the massive increase in deaths that we are seeing.
00:34:56
Speaker
The first stage was primarily a prescription drug stage overall.
00:35:02
Speaker
The second stage was a street drug, and now we're seeing the synthetic aspect of the street drug.
00:35:07
Speaker
And so what we're seeing is essentially a fentanyl epidemic.
00:35:13
Speaker
And, of course, the treatment has been on paper pretty simple, naloxone, which is the opioid mu antagonist overall.
00:35:23
Speaker
However, one needs very large doses for these to overcome fentanyl,
00:35:29
Speaker
and other types of synthetic opioid intoxications and poisoning, essentially.
00:35:36
Speaker
So one needs doses significantly over 2 milligrams in these individuals.
00:35:42
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.
00:35:59
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.
00:36:11
Speaker
So could you just reiterate, I mean, how would you would approach in terms of dosing these patients?
00:36:16
Speaker
Yes, I would repeat the doses every few minutes of naloxone.
00:36:23
Speaker
If there is some small degree of response,
00:36:28
Speaker
or even if there's no response, an individual suspected of an opioid overdose.
00:36:35
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.
00:36:48
Speaker
Oftentimes, these individuals, as I mentioned last time, may take other substances that are contaminated, not only the fentanyl,
00:36:58
Speaker
with what they think is heroin, but other substance I mentioned diphenhydramine.
00:37:03
Speaker
Quetiapine is also something I've seen quite a bit contaminated with our heroin.
00:37:08
Speaker
So all these substances don't respond to naloxone in a very favorable manner.
00:37:15
Speaker
That is at the usual dose of 0.2 to 2 milligrams IV.
00:37:18
Speaker
They may need much higher doses, and some of these substances, such as diphenhydramine and quetiapine, don't really respond to naloxone.
00:37:25
Speaker
And it would seem to me that with the appropriate interventions in a timely manner, most of these patients should not die.
00:37:33
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.
00:37:45
Speaker
Is that correct?
00:37:47
Speaker
That's correct.
00:37:48
Speaker
The irony is that it's been shown that patients
00:37:52
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.
00:38:18
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.
00:38:35
Speaker
So clearly, I mean, once you intervene, they're very salvageable.
00:38:41
Speaker
The problem is that a lot of these patients get to us too late.
00:38:44
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?
00:38:56
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.
00:39:11
Speaker
For example, if it was pure heroin,
00:39:13
Speaker
that would last for maybe a few hours, certainly less than six hours as far as the comatose aspect.
00:39:20
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.
00:39:30
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.
00:39:42
Speaker
And I think the other question I had for you is just any recommendations of the use of a naloxone drip?
00:39:48
Speaker
Usually, my practice is to whatever effective dose I had to use either half to two-thirds of that on an hourly basis.
00:39:56
Speaker
Is that usually what you would recommend?
00:39:58
Speaker
Yes.
00:39:59
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.
00:40:08
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
00:40:38
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
00:41:05
Speaker
salicylates can cause almost any type of acid-base disorder or mixed acid disorder other than a metabolic alkalosis.
00:41:17
Speaker
One has a pure metabolic alkalosis, that's probably the one thing salicylates don't, does not develop from salicylate poisoning.
00:41:26
Speaker
But just about everything else, in a sense, in terms of acid-base,
00:41:31
Speaker
One can initially, the biggest presenting sign of acute salicylate overdose that one can see right away is tinnitus or hard of hearing.
00:41:43
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.
00:41:54
Speaker
That could be a clue to very serious salicylate poisoning.
00:41:58
Speaker
So in almost all the cases of bad salicylate poisoning, hard of hearing is a major presenting sign.
00:42:04
Speaker
And in terms of a workup from a diagnostic standpoint, what are the labs that you would order?
00:42:08
Speaker
Okay, well, I would order the usual labs as far as basic metabolic profile, INR, CBC.
00:42:18
Speaker
Also, one other aspect are liver function tests or renal tests.
00:42:24
Speaker
UA is important to look because one may have to alkalinize the urine to pH of 7.5 or greater.
00:42:32
Speaker
So looking at the urine pH is somewhat important and salicylate.
00:42:36
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.
00:42:50
Speaker
And in terms of treatment, I think that you mentioned, obviously, always supportive care.
00:42:54
Speaker
So taking care of the airway, breathing, support.
00:42:57
Speaker
These patients can develop, I mean, different toxic cities in the lung.
00:43:00
Speaker
We can have some pulmonary edema.
00:43:02
Speaker
But these patients also are usually volume depleted.
00:43:05
Speaker
So starting with IV fluids is important.
00:43:08
Speaker
When is dialysis part of the picture?
00:43:12
Speaker
Well, first of all, decontamination can be important.
00:43:14
Speaker
If they come in within a few hours, activated charcoal at one gram per kilogram,
00:43:19
Speaker
can help improve the outcome quite a bit.
00:43:24
Speaker
As far as we do alkaline diuresis, urine alkalinization increases the elimination of salicylates.
00:43:36
Speaker
And so trying to get the urine pH to about 7.5 to 8.
00:43:40
Speaker
Hemodialysis does efficiently remove the salicylate and it can improve the acid base and electrolyte disorders in a sense.
00:43:49
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.
00:43:59
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
00:44:19
Speaker
all the clinical aspects deteriorate with INR, liver insufficiency, renal insufficiency, acute lung injury.
00:44:28
Speaker
If you cannot alkalinize the urine very well due to inability of sodium bicarbonate to be given in a sense.
00:44:35
Speaker
So these are some of the indications for salicylate ingestion and hemodialysis use.
00:44:42
Speaker
And I think that just an important reminder for our listeners is that
00:44:46
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?
Salicylate Intoxication
00:45:07
Speaker
Correct, and also have a low threshold for getting a salicylate level overall because it can look like a gastroenteritis,
00:45:16
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
00:45:38
Speaker
Excellent.
00:45:39
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.
00:46:06
Speaker
Getting the salicylate or acetaminophen levels can be key in those patients.
00:46:10
Speaker
Absolutely.
00:46:11
Speaker
So I guess the next big category is the cardiovascular drugs.
00:46:15
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.
00:46:27
Speaker
And I think that there's not one ED or ICU who doesn't deal with these patients on a yearly basis.
00:46:35
Speaker
I guess we could talk about them later.
00:46:38
Speaker
in a big lump together because they're very similar, but there might be some differences.
00:46:42
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?
00:46:50
Speaker
Yes, beta blockers are causing bradycardia and hypotension, although other aspects can occur with it.
00:47:01
Speaker
For example, propranolol can cause seizures.
00:47:04
Speaker
It can cause QRS widening.
00:47:07
Speaker
that can result in ventricular dysrhythmias.
00:47:10
Speaker
Hypoglycemia can develop in kids who've taken too much of the beta blocker.
00:47:15
Speaker
So other aspects can occur with it besides the hypotension and bradycardia.
00:47:22
Speaker
Bronchospasm can also develop in some of these individuals.
00:47:26
Speaker
The onset is usually within six hours, especially with beta blockers.
00:47:33
Speaker
overall but calcium channel blockers it's usually within eight hours.
00:47:37
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
00:48:02
Speaker
What are the first interventions that you would institute?
00:48:06
Speaker
And can you give us specific comments about the role and efficacy of atropine?
00:48:12
Speaker
Well, essentially decontamination, if seen within an hour or two, should be considered in both cases, beta blockers and calcium channel blockers.
00:48:23
Speaker
Standard ACLS treatment regarding bradycardia and hypotension is
00:48:29
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
00:48:59
Speaker
And so that aspect, you know, can be quite useful, but only as a transient measure.
00:49:08
Speaker
Vasopressors in the traditional manner, epinephrine, vasopressin even, phenylephrine, can occasionally be effective.
00:49:17
Speaker
They usually, patients usually don't respond to the dopamine or norepinephrine.
00:49:22
Speaker
What we've been using, particularly in calcium channel blockers, is high-dose insulin.
00:49:27
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
00:49:55
Speaker
and you can repeat a dose up to four to 10 milligrams.
00:50:00
Speaker
And so that could be quite effective.
00:50:02
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.
00:50:12
Speaker
where hypotension was refractory.
00:50:14
Speaker
So I think that just to summarize, I think this is valuable.
00:50:17
Speaker
Obviously, we start with fluids.
00:50:19
Speaker
Atropine, I mean, it can be utilized, but it's usually not as effective.
00:50:22
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.
00:50:31
Speaker
And I really try to keep the blood pressure perfusion.
00:50:34
Speaker
If the perfusion pressure is good, the heart rate becomes less relevant.
00:50:38
Speaker
And there is also...
00:50:40
Speaker
a significant amount of vasodilation that's going on and other reasons why the patient is very hypotensive, not only the bradycardia.
00:50:47
Speaker
Use depressors, as you mentioned.
00:50:49
Speaker
And then glucagon, effective for both, but much more effective for beta blockers, correct?
00:50:57
Speaker
Yes.
00:50:58
Speaker
Glucagon is effective for especially in individuals that respond to the fluid therapy.
00:51:03
Speaker
And insulin therapy, is that more effective for calcium gynoblockers?
00:51:08
Speaker
Yes, but it is potentially effective for beta blockers too.
00:51:11
Speaker
So you would use both.
00:51:12
Speaker
And then the lipid emulsion, as you mentioned, also has been utilized in calcium channel blocker toxicities.
00:51:18
Speaker
Can that be utilized also for beta blockers?
00:51:21
Speaker
Yes, it has been used for beta blockers, especially the lipid soluble beta receptor antagonists.
00:51:28
Speaker
And I think that the other interventions that are more heroic but have been utilized are transvenous pacing.
00:51:35
Speaker
Transcutaneous pacing is not usually as effective but can be utilized short term.
00:51:39
Speaker
And even some cases have described patients being put on ECMO for support that are arrested while these drugs are metabolized.
00:51:47
Speaker
But those are usually much more rare.
00:51:50
Speaker
And I think that with the interventions that you mentioned, usually most of these patients can be taken care of in the ICU.
00:51:56
Speaker
Yes, hemodialysis has been used for beta blockers with relatively limited volumes of distribution, such as atenolol, sodolol, and natolol.
Beta Blockers and Hemodialysis
00:52:07
Speaker
So that could also be, I think, a potential therapy to keep in mind.
00:52:10
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.
00:52:21
Speaker
That's correct.
00:52:22
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
00:52:48
Speaker
Basically, we still see cardiac glycosides.
00:52:51
Speaker
It's a naturally occurring toxin, so to speak.
00:52:54
Speaker
It's still in certain plants such as foxglove and the like.
00:53:00
Speaker
But the most common reason, the most common toxicities are usually with digoxin.
00:53:06
Speaker
And in terms of recognizing digoxin toxicity, you can get a digoxin level.
00:53:13
Speaker
But you had mentioned to us earlier that there are some arrhythmias that should make you think this is possible digoxin toxicity.
00:53:21
Speaker
Any comments on how the EKG might help you?
00:53:24
Speaker
Yes, bidirectional ventricular tachycardia may be somewhat diagnostic for it.
00:53:31
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?
00:53:56
Speaker
association with marked hyperkalemia and
00:53:59
Speaker
That should be a clue that a cardiac glycoside is involved.
00:54:02
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?
00:54:13
Speaker
Correct.
00:54:13
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,
00:54:24
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.
00:54:42
Speaker
And what about Digibind?
00:54:43
Speaker
I have never utilized it.
00:54:45
Speaker
I have had patients who we almost utilize it but have never really pulled the trigger.
00:54:51
Speaker
What are the thoughts?
00:54:51
Speaker
I mean, obviously, there's very dramatic stories of the first time Digibind was utilized.
00:54:56
Speaker
But what are the recommendations today for utilizing that therapy?
00:55:02
Speaker
Well, as mentioned, if you have elevated potassium over 5 millicrylons per liter in acute overdoses,
00:55:08
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,
00:55:36
Speaker
to other types of conventional ACLS type of therapy, that's where digoxin immune FAB fragments can be considered.
00:55:46
Speaker
Any other
Digoxin Toxicity Management
00:55:47
Speaker
comments on the cardiovascular drugs that you want to share with us, Jerry, before we move on to our last category of drugs?
00:55:54
Speaker
Not really.
00:55:55
Speaker
For the most part, they're supportive, supportive care.
00:55:59
Speaker
The local anesthetics can cause a variety of
00:56:03
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
00:56:31
Speaker
intoxications in the ICU and I think it's still important to recognize and treat them appropriately.
00:56:38
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.
00:56:51
Speaker
We still see it on occasion overall and its treatment
00:56:59
Speaker
can be quite complicated because there is no specific antidote per se.
00:57:04
Speaker
And one cannot really get blood levels per se of these substances.
00:57:09
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.
00:57:19
Speaker
And what would be the profile of a patient other than the history that would make you suspect?
00:57:24
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?
00:57:39
Speaker
Well, most of tricyclics have some anticholinergic properties.
00:57:42
Speaker
So dilated pupils can be seen, drowsiness, difficulty to arouse,
00:57:48
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.
00:58:04
Speaker
So, but oftentimes these patients will demonstrate some anticholinergic effects.
00:58:11
Speaker
So decreased bowel sounds is also may be evident along with respiratory depression.
00:58:18
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.
00:58:28
Speaker
And then an EKG is critical.
00:58:30
Speaker
And can you tell us how you use the EKG to direct your treatment?
00:58:35
Speaker
Certainly.
00:58:36
Speaker
The EKG is critical.
00:58:39
Speaker
QRS prolongation is one of the key signs.
00:58:44
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
00:59:07
Speaker
Oftentimes, there is additionally QTC prolongation over 500 milliseconds.
00:59:14
Speaker
And so if one has QRS prolongation, QTC prolongation, ventricular arrhythmia is a risk.
00:59:24
Speaker
And I think that these patients obviously merit admission to an ICU.
00:59:28
Speaker
And usually the indication traditionally has been to start sodium bicarbonate.
00:59:33
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.
00:59:45
Speaker
Can you comment on how you would treat these?
00:59:48
Speaker
Well, I do treat with sodium bicarbonate usually and try to attain a serum pH of 7.45 to 7.55.
00:59:53
Speaker
Try not to exceed 7.6 as an alkalinization pH.
01:00:00
Speaker
That can help decrease the QRS prolongation in this sense by blocking more or less the quinidine type effect.
01:00:08
Speaker
Now, you're right regarding hypertonic saline has been used for severe QRS whitening.
01:00:14
Speaker
We're talking over 160 milliseconds.
01:00:17
Speaker
That has not been responsive.
01:00:19
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.
Tricyclic Antidepressant Overdose
01:00:27
Speaker
So the mainstay would be just to alkalinize the blood, start the sodium bicarbonate, and monitor the patients aggressively.
01:00:35
Speaker
And if these patients do develop, I mean, ventricular tachycardias, are they more resistant to normal ACLS treatment?
01:00:42
Speaker
Is there anything else that we should be concerned about or doing?
01:00:45
Speaker
Well, that's where the fat emulsion may come in that has been used in a sense.
01:00:49
Speaker
Ventricular arrhythmias can be managed by the serum alkalinization and then antiarrhythmics.
01:00:55
Speaker
Lidocaine is often ineffective, but that can be used.
01:00:59
Speaker
Amiodarone and DC shock can be given, but they may be ineffective.
01:01:06
Speaker
Penetoyne used to be used and can be thought of for dysrhythmias error and responsive to these other measures.
01:01:14
Speaker
Magnesium overdrive pacing can be used for torsades.
01:01:20
Speaker
But lipid emulsion can be considered with refractory dysrhythmias, especially in the view of hypertension.
01:01:27
Speaker
And is there any role for dialysis in these toxicities?
01:01:31
Speaker
No, not really.
01:01:33
Speaker
Dialysis, these individuals or these drugs have very large volume distributions.
01:01:42
Speaker
They may even have high protein binding.
01:01:45
Speaker
And so dialysis doesn't really affect the elimination.
01:01:50
Speaker
So it's mostly supportive care and treating the underlying potential arrhythmias.
01:01:55
Speaker
Correct.
01:01:56
Speaker
Let's talk a little bit about lithium.
01:01:58
Speaker
It's still utilized, I think, in psychiatric treatments.
01:02:02
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.
01:02:15
Speaker
There's not only an acute, but also a chronic form.
01:02:18
Speaker
Could you tell us a little bit more about lithium, Jerry, and how do we encounter it today and in our practices?
01:02:24
Speaker
Yes.
01:02:24
Speaker
Well, of course, the major aspect of lithium, a major encounter, is with therapeutic use for bipolar disorder, in a sense.
01:02:35
Speaker
And that is the most common, and it is given chronically.
01:02:40
Speaker
Very rarely do we see an acute lithium overdose in a patient who is not on lithium.
01:02:46
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
01:03:10
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?
01:03:25
Speaker
Well, of course electrolytes particularly sodium urine analysis renal function sometimes thyroid function because chronic lithium therapy can cause hypothyroidism and
01:03:36
Speaker
overall, but the major thing to get is a serum lithium level and probably a serial lithium levels to look at the trend.
01:03:45
Speaker
Now, with lithium, what are the major dangers clinically?
01:03:49
Speaker
What are the, other than CNS alteration, what are things that we would worry about in our patients?
01:03:55
Speaker
Well, number one is the cost.
01:03:58
Speaker
For example, if a person has gastroenteritis that can predispose to lithium poisoning due to dehydration,
01:04:05
Speaker
So one looks for GI signs, nausea, vomiting, diarrhea, dehydration.
01:04:10
Speaker
Usually, moderate poisoning, severe poisoning will have some degree of nystagmus and tremors, along with change in mental status.
01:04:19
Speaker
And that's usually seen more with chronic exposures, in a sense.
01:04:26
Speaker
Abnormal temperature imbalance may occur, hyperthermia, in a sense, on EKG QTC prolongation can often be seen.
01:04:37
Speaker
hypoventilation can occur in concomitant with central nervous system depression.
01:04:44
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.
01:04:55
Speaker
Could you give us more details on that?
Lithium and SSRI Toxicity
01:04:58
Speaker
Yes, dialysis is one of the definitive treatments because it has a small volume distribution and it is water-soluble.
01:05:05
Speaker
and virtually no protein binding.
01:05:07
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.
01:05:21
Speaker
In the sense, if the lithium is greater than five millicolins per liter, probably more than four or increasing, it should be considered.
01:05:30
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.
01:05:53
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.
01:06:07
Speaker
What are the concerns that you have with SSRIs?
01:06:10
Speaker
I mean, they're very commonly prescribed.
01:06:12
Speaker
We talked a little bit about the serotonin syndrome last time we spoke, but any thoughts for our audience on SSRIs?
01:06:21
Speaker
Yes, as you stated, SSRIs actually are somewhat safer than tricyclics, which have replaced tricyclic depressants.
01:06:32
Speaker
And actually, tricyclics are somewhat safer than the MAO inhibitors, which it replaced back in the 1970s and 1980s.
01:06:39
Speaker
So these SSRIs are basically can cause some cardiac abnormalities, especially with QTC prolongations.
01:06:51
Speaker
PBCs, premature ventricular contractions, can occur.
01:06:56
Speaker
But most of these individuals that take SSRIs will experience only some mild toxicity, some nausea, mild CNS depression, vomiting, shakiness.
01:07:10
Speaker
Some degrees of sinus tachycardia with QTC prolongation can occur.
01:07:14
Speaker
Hyperreflexia can occur.
01:07:17
Speaker
So these are things that can be looked at.
01:07:20
Speaker
Anything in terms of specific therapies or suspicion?
01:07:23
Speaker
I mean, usually these are shorter-lived, and once we stop them and provide supportive care, usually patients do well, correct?
01:07:30
Speaker
Correct.
01:07:31
Speaker
Hemodialysis is usually not effective.
01:07:35
Speaker
The lipid motion therapy has been used for certain extraordinarily high, almost gargantuan ingestions of SSRIs.
01:07:46
Speaker
It has been used for bupropion, for example, and quetiapine overall.
01:07:53
Speaker
But the treatment for the most part is supportive care, benzodiazepines if seizures occur and the like.
01:08:00
Speaker
There's no specific antidote.
01:08:02
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
01:08:10
Speaker
to more toxins and other treatments, but we chose to deliberately focus on some of the more common drugs that clinicians might encounter.
01:08:21
Speaker
And I wanted to maybe close the podcast at this moment.
01:08:27
Speaker
And we've talked about last time we had some questions for you.
01:08:30
Speaker
Today I have a couple more questions to close with a topic not related to toxicology.
01:08:35
Speaker
Would that be okay?
01:08:37
Speaker
Of course.
01:08:38
Speaker
So last time I asked you about a book, today I wanted to know about your music taste.
01:08:43
Speaker
And it's interesting because you did mention a biography and a genius musician.
01:08:48
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?
01:08:55
Speaker
But let's suppose it's an album.
01:08:57
Speaker
Which one would it be?
01:08:59
Speaker
Well, I mentioned last time that the Hot 5 and Hot 7 with Louis Armstrong are something I listen to all the time.
01:09:06
Speaker
But also...
01:09:07
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.
01:09:20
Speaker
And so they really play all their hits and their music on the old BBC program that they used to have.
01:09:31
Speaker
And there are two parts to it.
01:09:32
Speaker
Each disc has like 25 different songs on it.
01:09:37
Speaker
It's really incredible if I had one thing to bring, that would be it.
01:09:41
Speaker
So I'll put that on the show notes.
01:09:42
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.
01:09:53
Speaker
Like my teenage son, I mean, knows the songs, enjoys them, and they've been around for a long time.
01:09:59
Speaker
But there's a reason why people still enjoy them because they're
01:10:02
Speaker
They're very, very special.
01:10:03
Speaker
So I'll definitely put that in the show notes.
01:10:04
Speaker
And I think it's a great selection.
01:10:06
Speaker
So the Beatles on the BBC.
01:10:09
Speaker
My last question relates to failure.
01:10:12
Speaker
And I think that we're always very fearful of failure.
01:10:16
Speaker
And I think don't like to talk about our failures.
01:10:19
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.
01:10:25
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.
01:10:33
Speaker
Well, when I finished my residency, I wanted to do toxicology.
01:10:37
Speaker
And actually, there are only very few toxicology programs back in 1984 that one could do a fellowship in and get boards in.
01:10:47
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
01:11:14
Speaker
And now, 35 years later, we have over 50 fellows that graduated from our program.
01:11:20
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.
01:11:30
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.
01:11:40
Speaker
Yes, it's very satisfying.
01:11:42
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.
01:11:50
Speaker
Well, everything happens for a reason.
01:11:52
Speaker
And I think it's what we do with things that happen to us that ultimately matters.
01:11:56
Speaker
So I think this is a great place to stop.
01:11:58
Speaker
Jerry, again, thank you so much for your time, not once but twice in the last couple of weeks.
01:12:04
Speaker
I mean, this two-part toxicology series, I think, has tremendous amount of pearls,
01:12:10
Speaker
and very applicable and very useful information for our bedside clinicians.
01:12:17
Speaker
So I look forward to maybe talking about other topics or more toxicology topics with you and the podcast in the future again.
01:12:23
Speaker
And thanks so much for your time.
01:12:26
Speaker
Thank you very much.
01:12:27
Speaker
Anytime, please call.
01:12:30
Speaker
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01:12:34
Speaker
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01:12:40
Speaker
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01:12:44
Speaker
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