Corinn Cross, MD (Host): This is Pediatric Insights, Advances, and Innovations with Children's Health, where we explore the latest in pediatric care and research.

I'm your host, Dr. Cori Cross. Today, we will discuss how acetaminophen can induce metabolic acidosis in children. With us today is Dr. Jyothsna Gattineni. She is the Division Chief of Pediatric Nephrology at Children's Health and an Associate Professor at UT Southwestern.

Dr. Gattineni, thank you so much for joining us today.

Jyothsna Gattineni, MD: Thank you for having me.

Host: So before we dive into this topic, can you share a bit about the Nephrology Department at Children's Health? Tell us a little bit about your team of experts and the wide range of conditions you treat at Children's Health.

Jyothsna Gattineni, MD: Sure. We have around 10 pediatric nephrologists at Children's and UT Southwestern right now and we do treat a wide range of conditions that you just mentioned and these can encompass starting from prenatal consults to congenital anomalies of kidney and urinary tract, hypertension, electrolyte imbalances, autoimmune kidney disease, acute and chronic kidney disease, acute and chronic kidney replacement therapy, and kidney transplantation among others.

Host: You obviously treat a wide range of nephrotic conditions, but let's discuss something that's really relevant to all pediatricians and parents. Acetaminophen induced acidosis. And for those of us listening who aren't aware, the brand name of acetaminophen, the common brand name at least, is Tylenol, which is obviously a very common medication for children to take. So tell us, Dr. Gattineni, what is acetaminophen induced acidosis, and why should doctors be aware of this?

Jyothsna Gattineni, MD: I would refer from here on out acetaminophen as Tylenol because I think that's what most parents will relate to. The physicians also relate to that very well. So acute Tylenol overdose is well known to physicians and results in severe and potentially life threatening liver disease. That's well known. We study about that in the medical school. We've seen patients over our journey in training and in practice. However, what I would like to talk about today is Tylenol induced acidosis.

So, this is rare and significantly under diagnosed condition. And this is because of long term use of Tylenol, and it's usually seen in the hospital. So, I would first preface by saying, parents, not to worry about this at home, because there are certain risk factors that your child needs to have before they can develop this. And the risk factors include female gender, malnutrition, infection, antibiotic use and a few antibiotics that are particularly make this susceptible, kidney failure or renal failure and pregnancy.

What happens in these patients who are susceptible, is that long term use of Tylenol; most importantly, at the therapeutic doses, that means the doses that are actually prescribed and are okay to prescribe and use; that in the long term, these patients have the predisposition to develop metabolic acidosis. And this is described in hospitalized children or adults.

Host: Now, when you talk about prolonged use, is there a specific length of time that you see as a threshold?

Jyothsna Gattineni, MD: Unfortunately, no. There are more than 50 cases that have been described with this condition, and each case varies because there are risk factors that keep adding on to the Tylenol. So it could be five, six days of regular dosing of Tylenol, or there are patients who have taken it for two, three weeks, on top of their risk factors.

Host: So you mentioned some case studies. Are there ones that you feel our listeners should be particularly aware of?

Jyothsna Gattineni, MD: So there are, if you actually Google and say pyroglutamic acidosis or do it in PubMed, which is mostly used by physicians, you can see pyroglutamic acidosis and you will get a list of case reports and case theories that have been published.

Host: That's very interesting. And so it sounds like there are children who are predisposed to this, that the general parent having the run of the mill child probably is not going to come across this. For the pediatricians, what signs and symptoms should we be looking for if we have a female patient who happens be on antibiotics and taking Tylenol for a little bit of time? What is it that we're looking for?

Jyothsna Gattineni, MD: I can tell you this, we ourselves published a case report recently about this and this was about a patient who presented to the hospital and was noted to have metabolic acidosis and this is primarily for the physicians. So these patients, when you encounter a patient with metabolic acidosis, which has high anion gap, of course we'll all do a workup for high anion gap metabolic acidosis.

And most of you might be very familiar with the mnemonics that are commonly used like MUDPILES and KUSMALE. But more recently, this new mnemonic, which is called GOLD MARK, which stands for like glycols, ethylene and propylene glycol overdose, O stands for oxyprolene, or pyroglutamic acid. L stands for lactate, D stands for D lactate, M for methanol and other toxins, A for aspirin, R for renal failure, and K for ketones.

And again, this is easily available on the web resources, it's GOLD MARK mnemonic. So one, if you encounter a patient with increased anion gap metabolic acidosis, you should go through this and work the patient up for high anion gap metabolic acidosis. And the symptomatology would be, you would notice that in a patient who has been hospitalized, obviously, and has increased respiratory rate because they're compensating for metabolic acidosis.

That would be the symptomatology that you would notice in a patient. And laboratory workup will show high anion gap metabolic acidosis, and at that point you will do the workup, including urine studies, which will help you, narrow down your differential.

Host: That makes a lot of sense. So, do you feel that the parents have a role in preventing this, acetaminophen acidosis or is it really just on the medical care expert that if the child comes in that we keep this on our differential diagnosis if we're seeing this high anion gap, metabolic acidosis with a compensatory or compensating respiratory rate.

Jyothsna Gattineni, MD: I would say that parents are our partners when we take care of children. So, they would be aware of how much Tylenol their child is getting, but this becomes more of a physician responsibility to notice these things and look for metabolic acidosis and initiate the workup when you have a malnourished child, young lady who has kidney failure and who has infection and you're having to give a prolonged course of Tylenol, as in four, five, six days of Tylenol, even at just therapeutic doses.

Host: That makes sense and that's a very good point. So this is at therapeutic doses. This isn't the same thing that we think about as pediatricians where a parent is giving multiple medications that happen to have Tylenol in them and not realizing that they gave a cough medicine that also had Tylenol and then they gave a decongestant that also had Tylenol and that they're giving multiple doses of the same medication. This is where they're taking it completely the way they should and their body is just not reacting.

Jyothsna Gattineni, MD: Absolutely prescribed therapeutic doses of Tylenol can cost us in high risk patients.

Host: So before we wrap up, is there anything else you'd like to share? And could you summarize the take home message for our listeners today?

Jyothsna Gattineni, MD: I would say that one has to have a high clinical suspicion in high risk patient so that you can diagnose this, you can call it pyroglutamic acidosis or Tylenol induced metabolic acidosis. So you can diagnose this in a timely fashion and you can initiate effective treatment. And what is effective treatment is first withholding the offending agent, ie Tylenol here and there are case reports where they have used an acetylcysteine empirically that seems to expedite the process.

Of course, we don't have randomized controlled trials to say what the effect would be, but the side effects seem to be minimal and we can use an acetylcysteine.

Host: Right, and that would make sense since that's what we use for the Tylenol overdose itself.

Jyothsna Gattineni, MD: That is correct. Yes.

Host: And then for follow up, do these patients require any additional follow up and I'm assuming they're at risk for this in the future if they've had it once.

Jyothsna Gattineni, MD: Unfortunately as I said, there are not thousands of patients that are described. I'm sure lots more patients have this and it is like I mentioned earlier, it's an underdiagnosed condition. I would say, again, it has to be a perfect storm. You have to have all the risk factors and you need to have a prolonged course of Tylenol. So you're going to need Tylenol for a day or two and you don't have the risk factors, you don't need to worry about it. But if you do, then you have to be watchful and get your blood test checked to see what your acid base balance looks like.

Host: That all makes so much sense. Dr. Gattineni, thank you so much for being here with us today and educating our listeners on such an important topic. It was a real pleasure to speak with you.

Jyothsna Gattineni, MD: Thank you so much for having me.

Host: To learn more about acetaminophen induced acidosis or other nephrology topics, please visit childrens.com/nephrology. That's childrens.com/nephrology. If you found this podcast helpful, please rate, review, and share this episode, and please follow Children's Health on your social channels. I'm your host, Dr. Cori Cross, and I just want to thank you for listening to this episode of Pediatric Insights, Advances, and Innovations with Children's Health, where we explore the latest in pediatric care and research.