Episode 46 — Obstetric Pharmacology and Fetal Assessment With Mike Hofkamp
Highlights
- Obstetric Pharmacology and Fetal Assessment
Summary:
Dr. Mike Hoffkamp is a clinical associate professor at Texas A&M University Health Sciences Center College of Medicine and the director of obstetric anesthesia at Scott and White Medical Center Temple. Today we're going to talk about obstetric pharmacology and fetal assessment so what do you think why don't we start with pharmacology and go from there. The first thing I'd like to talk about is our inhalational agents that we use in the operator room.
Transcript:
Speaker 2
Alright folks let's get on with the main show I'm thrilled to have back with me today Dr. Mike Hoffkamp who is as you probably remember clinical associate professor at Texas A&M University Health Sciences Center College of Medicine and the director of obstetric anesthesia at Scott and White Medical Center Temple and we had an overview last time of some maternal physiology and now today we're going to get into a little more of a sub area of OB anesthesia and we're going to talk about obstetric pharmacology and fetal assessment Mike welcome back to the show.
Speaker 1
Thank you very much for having me Judd.
Speaker 2
So the way I think we can approach this let's we'll spend a bunch of time on pharmacology and then we'll also look at some issues of fetal assessment so what do you think why don't we start with pharmacology and go from there.
Speaker 1
Okay so the first thing I'd like to talk about is our inhalational agents that we use in the operator room. Now obviously the inhalational agents are going to be rapidly transferred across the percent of the fetus and inhalational agents have been associated with lower app guard scores particularly when you have longer induction to delivery times so the key point remember for (Time 0:02:26)
- C-Section Anesthesia
Summary:
Inhalational agents on the uterine tone will relax the uterus. Sometimes this is advantageous when you have a situation where the urs needs to be relaxed like an uterine inversion or if you really need to get a fetus out. This can cause diffusion hypoxia in the infant so any neonate that is exposed to nitrous oxide prior to delivery should have supplemental oxygen immediately after delivery.
Transcript:
Speaker 2
Okay now what about the effect of inhalational agents on the uterine tone.
Speaker 1
Okay well inhalational agents on the uterine tone will relax the uterus and sometimes this is advantageous when you have a situation where the urs needs to be relaxed like an uterine inversion or if you really need to get a fetus out but this is obviously problematic when you're trying to get the urs contract after the baby's out. I won't steal the thunder from a later lecture of our C-section anesthesia but in general inhalational agents will relax the uterus.
Speaker 2
Okay how about other anesthetic drugs.
Speaker 1
So nitrous oxide is the other drug we'll use during journal anesthesia and sometimes just for supplemental allergies you have during a C-section and this can cause diffusion hypoxia in the infant so any neonate that is exposed to nitrous oxide prior to delivery should have supplemental oxygen immediately after delivery. (Time 0:03:57)
- Nitrous Oxide and Hypoxemia
Summary:
Other anesthetic drugs that we need to think about are benzodiazepines. Diasipam is lipophilic and crosses the placenta rapidly. Lorazepam is less lipophilic but midazolam is most likely to use in the operating room.
Transcript:
Speaker 1
Well just this like this like it sounds the the nitrous oxide goes across the placenta goes into the into the into the fetus the fetus will have some nitrous oxide in its bloodstream in its stores and when it's delivered it will it will excrete that nitrous oxide through their lungs they'll breathe it out and that crowds out the oxygen in the alveoli and it could potentially cause hypoxemia. Got it.
Speaker 2
All right so we've talked about inhalational agents including nitrous what about other anesthetic drugs that we need to think about.
Speaker 1
So benzodiazepines are another drug to think about typically we don't really give benzodiazepines around the time of delivery but they can be given in very select circumstances. Things to remember that drugs like diasipam is lipophilic and crosses the placenta rapidly. Lorazepam is less lipophilic and in fact midazolam the drug that we're most likely to use in the operating room is more polarized and crosses the placenta less. So if you make the judgment call that you want to give your laboring patients or your patient in the operating room of benzodiazepine, midazolam due to its polarity is probably the best choice.
Speaker 2
Okay that's good to know. (Time 0:05:17)
- Propofol and Morphine
Summary:
Mopyridine is associated with neonatal centro-nurist system and respiratory depression. Morphine and fentanyl rapidly cross the placenta. Remifetinol because of its ester group is rapidly metabolized. It is an ideal drug for to give an induction for a C-section.
Transcript:
Speaker 2
Okay that's good to know. Now we should probably point out as you mentioned earlier we're making a distinction here between actual C-section anesthesia which will do a separate talk on and right what we're talking about now is obstetric pharmacology. So this could be for example a woman who's pregnant coming to the operating room for and happened ectomy. It doesn't mean we're not we're not dealing specifically with a pregnant woman having a C-section.
Speaker 1
That's very that's correct. Thank you for making that point. All right great.
Speaker 2
So we talked about benzos anything else how about propofol?
Speaker 1
Let's see here. So let's let's talk about opioids.
Speaker 2
Okay let's start with opioids.
Speaker 1
So opioids the pyridine is associated with neonatal centro-nurist system and respiratory depression. We don't usually give mopyridine as a pure analgesic we usually give it for for shivering but it's useful to remember that if you're going to give mopyridine the pregnant patient there again it's going to be associated these bad things. Morphine and fentanyl rapidly cross the placenta. Remifetinol because of its ester group is rapidly metabolized and it is an ideal drug for to give an induction for (Time 0:06:35)
- Can Propofol Cross Placenta?
Summary:
propofol obviously is lipophilic it can cross the placenta. Apgar scores are higher in thiopental inductions compared to propofol inductions. The effects of propofol are going to be short-lived and not realized unless the fetus is delivered with the propofol in its bloodstream. With medazlam that is a theoretical risk of tragedy and acidity so we do avoid medazlam in the first and second trimesters.
Transcript:
Speaker 1
All right I'm sorry let's I'll get back to your propofol question. Sure. So propofol obviously is lipophilic it can cross the placenta. Interestingly enough a historical tidbit is Apgar scores are higher in thiopental inductions compared to propofol inductions. That's kind of a mood point now that thiopental isn't commercially available but for c-section aesthetics obviously propofol is going to cross placenta it's going to have some effect on the fetus. The volatile is probably going to have just as much effect for as far as non c-section aesthetics just like the opioids we talked about the effects of propofol are going to be short-lived and not realized unless the fetus is delivered with the propofol in its bloodstream.
Speaker 2
Great. Now how about very early in pregnancy my first trimester for example is there worry at all about any teregienic effects of any of these propofol benzos would you avoid them in a woman having a non-related surgery but who happened to be pregnant?
Speaker 1
So with with medazlam that is a theoretical risk of tragedy and acidity so we do avoid medazlam in the first and second (Time 0:08:54)
- Is There a Connection Between Pregnancy and Lidocaine?
Summary:
There is some data out there though I don't think it's very definitive at all about the potential connection of Tylenol use in pregnant women. It can lead to decreased alpha-1 acid glycoprotein levels which results in a higher concentration of free lidocaine. Local aesthetics we can talk about that just for a moment here. So obviously pregnant patients are going to be more sensitive the effects of local aesthetics like we talked about before in the internal physiology lecture. All right great and as far as I know no no issues with TylenOL is that right? No no issues at all of Tylanol not for the fetus at least.
Transcript:
Speaker 2
All right great and as far as I know no no issues with Tylenol is that right? No no issues at all of Tylenol not for the fetus at least. Okay I know there is some data out there though I don't think it's very definitive at all about the potential connection of Tylenol use in pregnant women and later development of asthma and children but I certainly don't think it's been established to the point where anybody's recommending against using Tylenol while pregnant.
Speaker 1
Yeah I mean like that's that's a theoretical concern but in my practice I think that Tylenol is a very reasonable drug that we give all the time to pregnant people.
Speaker 2
Great anything else in the anesthetic drug category anything that we should be thinking about?
Speaker 1
Well local aesthetics we can talk about that just for a moment here. So obviously pregnant patients are going to be more sensitive the effects of local aesthetics like we talked about before in the internal physiology lecture. One of the interesting things about pregnancy is that it can lead to decreased alpha-1 acid glycoprotein levels which results in a higher concentration of free lidocaine. So I give a bullish glyocaine to (Time 0:11:21)
- What Is an Oxytocin Drug?
Summary:
On the labor and delivery unit it's dosed by protocol. If you give too much oxytocin you can get uterine hyperstimulation. This is where the uterus can contract so forcefully and frequently that fetal blood flow is interrupted. Tributoline is a beta agonist and it can also be used as an alternative to oxytocin.
Transcript:
Speaker 1
Correct the pitocin is the trade name. Okay. But the generic name is oxytocin. Great. And interesting thing about oxytocin is that on the labor and delivery unit it's dosed by protocol so the obstetric staff will write an order for oxytocin infusion and the nurses will follow a standardized protocol and so they're not calling the obstetric staff or residents every single five minutes to figure out whether they need to go up or down. One of the interesting things on the labor and delivery unit in particular in particular is that if you give too much oxytocin you can get uterine hyperstimulation. This is where the uterus can contract so forcefully and frequently that fetal blood flow is interrupted and so when you have uterine hyperstimulation you really have to number one stop the oxytocin infusion and two possibly even consider giving a drug like tributoline to stop the contractions.
Speaker 2
And tributoline is a beta agonist is that right?
Speaker 1
Tributoline is a beta agonist and it can (Time 0:14:24)
- Methyl Organovine
Summary:
Tributoline is a beta agonist and it can also here's the one thing you should probably remember about tributoline if you're going to be taking the board exam it can cause pulmonary edema. Methyl organovine has been associated with intrastrieval hemorrhage so you want to avoid methyl organovine in patients who have those conditions. And this is the medication that's often referred to as methergin.
Transcript:
Speaker 1
Tributoline is a beta agonist and it can also here's the one thing you should probably remember about tributoline if you're going to be taking the board exam it can cause pulmonary edema that seems to be one of the favorite things they ask about tributoline. So tributoline equals pulmonary edema. It can also cause hyperglycemia and hypokalemia as it is a beta agonist.
Speaker 2
Okay so those are key side effects to know it's a uterine relaxant as you said and so if you get into hyperstimulation from oxytocin it's essentially an antidote for that.
Speaker 1
Yes and let me talk about methyl organovine. So this is a drug that causes the eaters to contract a lot and this drug is reserved for the use of a pretty significant post-parum hemorrhage and it should never be given IV because that could cause some really really bad effects it's always given IM and it is contraindicated in preeclampsia. So someone has gestational hypertension or preeclampsia. Methyl organovine has been associated with intrastrieval hemorrhage so you want to avoid methyl organovine in patients who have those conditions.
Speaker 2
And this is the medication that's often referred to as methergin.
Speaker 1
Correct that's the yes. (Time 0:15:32)
- Preeclampsia - Methyl Organovine
Summary:
Methyl organovine has been associated with intrastrieval hemorrhage so you want to avoid methyl organovine in patients who have those conditions. Hemabate is a good drug for someone who has preeclampsia but it's a bad drug for someone Who's got asthma because it can cause bronchoconstriction. And this is the medication that's often referred to as methergin.
Transcript:
Speaker 1
Yes and let me talk about methyl organovine. So this is a drug that causes the eaters to contract a lot and this drug is reserved for the use of a pretty significant post-parum hemorrhage and it should never be given IV because that could cause some really really bad effects it's always given IM and it is contraindicated in preeclampsia. So someone has gestational hypertension or preeclampsia. Methyl organovine has been associated with intrastrieval hemorrhage so you want to avoid methyl organovine in patients who have those conditions.
Speaker 2
And this is the medication that's often referred to as methergin.
Speaker 1
Correct that's the yes.
Speaker 2
Okay so as you said used to control post-partum hemorrhage in the sense that it's going to cause contraction of the uterus and therefore squeezing down on those blood vessels but should be given IM only and has the side effect of hypertension which you wouldn't want in someone with preeclampsia.
Speaker 1
That's correct. So another drug that we can use to cause use contract our prostaglandins and the trade name for the drug that we use in the operating room is hemabate. Now this is a good drug for someone who has preeclampsia but it's a bad drug for someone who's got asthma because it can cause bronchoconstriction. So someone has asthma do not give them a hemabate.
Speaker 2
Now I remember that sometimes they ask a question where they want where the answer is hemabate but they don't tell you the name hemabate they give you the and you're gonna have to remind me but I think it's something like five methyl something or other right. (Time 0:16:06)
- Is Prostaglandin F2 Alpha a Tocolytic Drug?
Summary:
Prostaglandin F2 alpha is known as hemabate. Magnesium sulfate can be used as a tocolytic. It can potentiate the effects of non-depolarizing neuromuscular blockers. So if you have a patient who is on mag and you are trying to control postpartum hemorrhage or could be for after a regular delivery that you would have availableyou mentioned the important side effects methogen contraindicated for preeclampsia hemabate contraindication in asthmatics. Yes.
Transcript:
Speaker 1
hemabate.
Speaker 2
Now I remember that sometimes they ask a question where they want where the answer is hemabate but they don't tell you the name hemabate they give you the and you're gonna have to remind me but I think it's something like five methyl something or other right.
Speaker 1
That's prostaglandin F2 alpha I believe.
Speaker 2
Prostaglandin F2 alpha okay not five methyl I was wrong there but it was an F2 alpha was what I was thinking. So prostaglandin F2 alpha they may have that as an answer choice so you have to recognize that hemabate is no error that prostaglandin F2 alpha is known as hemabate. Yeah. All right so those are two drugs often present in the operating room for a C-section to to control postpartum hemorrhage or could be for after a regular delivery that you would have available you mentioned the important side effects the contraindications methogen contraindicated for preeclampsia hemabate contraindicated in asthmatics. Yes.
Speaker 1
All right.
Speaker 2
Are there other tocolytic drugs that we should talk about?
Speaker 1
So let's talk about the magnesium sulfate. Okay. So that can be used as a tocolytic it's usually used as as a pre-claptic drug to prevent seizures but it can be used as a tocolytic. One of the things to remember about magnesium sulfate is it can potentiate the effects of non-depolarizing neuromuscular blockers. Yep. So if you have a patient who is on mag and you (Time 0:17:39)
- MAC Increases Neuromuscular Blocker Side Effects
Summary:
Magnesium sulfate reduces the minimum alveolar concentration. So decreases MAC increases the action of non-depolarizing neuromuscular blockers. The other thing that's asked about mag a fair amount are the levels of mag at which you start to see side effects. And so you got to monitor the patients for signs of toxicity and so you'll see the obstetricians out with their reflex hammers.
Transcript:
Speaker 1
lot. Another interesting thing about magnesium sulfate that's asked a lot is that it reduces the minimum alveolar concentration.
Speaker 2
Right. So decreases MAC increases the action of non-depolarizing neuromuscular blockers. The other thing that's asked about mag a fair amount are the levels of mag at which you start to see side effects.
Speaker 1
Yes. And so you got to monitor the patients for signs of toxicity and so you'll see the obstetricians out with their reflex hammers and that's one of the first things to go is the dependent reflexes. Now later on you're going to see you're going to see a respiratory depression very late. You're going to see altered mental status very late and you really definitely want to monitor for for those things and going to the lab is going to take too long. You really want to be able to identify these things at the (Time 0:19:21)
- Is It Neuroprotective for Preterm Labor?
Summary:
The most common use of magnesium in a pregnant woman would be treating someone who is pre-aclamtic and then the it's also used as you said for tocolysis. Typically not typically we'll use tributoline. Tributolines a little bit quicker and has a different mechanism of action that's more amenable to stopping the contractions.
Transcript:
Speaker 1
Typically not typically we'll use tributoline. Okay. Tributolines a little bit quicker and has a different mechanism of action that's more amenable to stopping the contractions.
Speaker 2
All right so the most common use of magnesium in a pregnant woman would be treating someone who is pre-aclamtic and then the it's also used as you said for tocolysis and I believe and I'm stretching here but that there is some data in the obstetric literature from magnesium as a neuroprotective agent.
Speaker 1
It is it is it is you're absolutely right so it's neuroprotective for the preterm fetus and so when magnesium sulfate is giving for the indication of preterm labor it can be stopped immediately after delivery. So it's important to make that distinction with the obstetric the obstetric staff because if a patient is on magnesium sulfate for pre-clampsia they have to get it long after delivery but if it's for preterm labor and it's neuroprotection you can stop that right or you should you absolutely should stop it right after delivery so the mother doesn't have any effects from (Time 0:21:33)
- Is It Neuroprotective for Preterm Labor?
Summary:
magnesium sulfate is giving for the indication of preterm labor it can be stopped immediately after delivery. calcium child walkers to like nephetopane can be used as a tocolytic. Let's move on to anti-seizure drugs. These drugs are sometimes given and they have implications for pregnant patients. We really want to avoid giving phenotone during organogenesis in the first trimester.
Transcript:
Speaker 1
It is it is it is you're absolutely right so it's neuroprotective for the preterm fetus and so when magnesium sulfate is giving for the indication of preterm labor it can be stopped immediately after delivery. So it's important to make that distinction with the obstetric the obstetric staff because if a patient is on magnesium sulfate for pre-clampsia they have to get it long after delivery but if it's for preterm labor and it's neuroprotection you can stop that right or you should you absolutely should stop it right after delivery so the mother doesn't have any effects from that.
Speaker 2
Right clearly once the baby's out there's no advantage to the baby to continue giving it to the mother. Correct. All right are there other medications in terms of tocolytics that we should talk about?
Speaker 1
Just briefly calcium child walkers to like nephetopane can be used as a tocolytic. Okay. What about?
Speaker 2
Okay let's yeah I'm sorry. No go ahead.
Speaker 1
Let's move on to anti-seizure drugs. These drugs are sometimes given and they have implications for pregnant patients. So phenotone is an anti-convulsant it's a very effective anti-convulsant but it's also a competitive inhibitor of vitamin K and so we really really want to avoid giving phenotone during organogenesis in the first trimester and you (Time 0:22:03)
- Mechanisms of Placental Transfer
Summary:
Drugs that don't cross the placenta tend to be ionized polarized and not amenable to crossing membranes. Drugs like lycopyrillate, heparin, succinylcholine, non-depolarizing, muscle relaxants. The most important member of the team would be the mother herself and deciding what is best for for her health.
Transcript:
Speaker 1
ears.
Speaker 2
So none of these sound good are there any anti-seizure medications that are safer during pregnancy?
Speaker 1
You know not to my knowledge.
Speaker 2
So essentially it's a risk benefit analysis someone who's pregnant with a bad enough seizure disorder may have to be on these and then you're just running the risk of the fetal abnormalities but you have to kind of as you said get a multidisciplinary panel together and make a decision obviously along with the most important member of the team would be the mother herself and deciding what is best for for her health.
Speaker 1
Yes so real briefly let's talk about mechanisms of placental transfer. Great so so in general there are drugs that cross the placenta and there are drugs that don't cross the placenta. So drugs that don't cross the placenta tend to be ionized polarized and not amenable to crossing membranes like drugs like lycopyrillate, heparin, succinylcholine, non-depolarizing, muscle relaxants. (Time 0:25:30)
- Drug Transfer
Summary:
A drug that has a high proportion of unionized drug and maternal plasma is going to cross easier. Some drugs have transport proteins on the placenta that will help transport across. And along those lines there's something called ion trapping, which can happen with lidocaine.
Transcript:
Speaker 1
Also it depends also there's a relationship between the size of the drug and how easily it's going to cross the placenta. So drug that's less than a thousand daltons is going to have increased transfer drug that's more than a thousand daltons is not. A drug that has a high proportion of unionized drug and maternal plasma is going to cross easier than a drug that has a higher proportion. And there are some drugs that have transport proteins on the placenta that will help transport across and if a drug doesn't have these proteins it's not going to be as transferred as much. And along those lines there's something called ion trapping and so ion trapping is something that's tested quite frequently. What happens is that you have an unionized drug on the maternal side and due to a concentration gradient that will cross the placenta and once it crosses the placenta the placenta tends to be more of an acidic environment. And so if you have a pKa that's closer to that's close to 7.4 which is the physiologic state of plasma that drug when it crosses into the fetal circulation is going to be protonated and thus ionized and it's going to be so-called trapped in the fetus. And so this can happen with this can happen very easily with lidocaine. (Time 0:26:57)
- Amniotic Fluid
Summary:
The anti- seizure medications like Fennetone are pregnancy category D warfarin is indeed up pregnancy category X though as you heard from Mike there might be a time when you do decide to use it. It's composed of fetal urine lung fluid skin transudate and water that is filtered across the amniotic membranes. Something it sounds like something you'd want to be swimming in huh?
Transcript:
Speaker 2
So okay so maybe that's more of a D than an X. Yeah but he certainly isn't X during the first trimester of pregnancy. Okay interesting. All right so good those are the FDA categories. Hey folks it's Jed Hoppin in here I did just look this up after I finished the interview with Mike and we were correct that the anti- seizure medications like Fennetone are pregnancy category D warfarin is indeed up pregnancy category X though as you heard from Mike there might be a time when you do decide to use it but in general X meaning you would hardly ever use it or you certainly would never want to use it unless you had as Mike said of a really multi-disciplinary board along with the patient thinking about it and making a decision including talking to your legal representatives as well. All right let's get back to the interview. So Mike one thing we hear a lot about is amniotic fluid. Tell me about amniotic fluid and what we need to know about that.
Speaker 1
So the amniotic fluid it's composed of fetal urine lung fluid skin transudate and water that is filtered across the amniotic membranes. It can also contain electrolytes proteins and desquimated fetal cells. Something it sounds like something you'd want to be swimming in huh? (Time 0:33:27)