Cause of neonatal brain injury in HIE?// Diagnosis: exam and labs

Today we're going to talk about HIE or hypoxic ischemic encephalopathy or basically when a baby's brain doesn't get enough oxygen at birth and it somehow then affects that brain's function. As you can imagine HIE is a major cause of neurological disabilities in term babies. In fact in developed countries it can affect up to about eight out of a thousand births and in underdeveloped countries it can affect up to 26 infants out of a thousand births. I also want to make a quick point that even though HIE is a type of neonatal encephalopathy there are many other disease processes that can cause encephalopathy. So like meningitis or herpes encephalitis or metabolic diseases a myriad of other conditions. Today I'm just going to be focusing on HIE. So we decided since this video was so long to split it into two parts. So today I'm just going to be talking about the pathophysiology of HIE. So what actually causes HIE as well as the diagnosis of HIE. So including the importance of the neurological exam as well as blood gases. In the next video we'll be talking about treatment of HIE or more specifically hypothermia therapy as well as all the supportive treatment that we give while we are calling babies. So let's start with the pathophysiology. As you all know adequate cerebral blood flow is very tightly regulated to make sure that the brain is always receiving enough oxygen and enough glucose. This is to make sure that the cells in the brain are always getting the energy that they need. If in utero or during delivery the brain cells lack oxygen so there's hypoxia or lack blood so there's ischemia which obviously would also lead to lacking oxygen. Then those brain cells may not have the energy that they need to function. And therefore if they are not functioning correctly then they could be injured. This is the basis of the encephalopathy or injury to the brain. Remember the baby's body just like any mammal will do whatever it can to preserve the function of the absolutely vital organs. So if in a baby's body the baby is not getting enough oxygen then the body as much as possible will try to shunt as much blood as possible to the brain and the heart which are obviously completely vital organs every single second as opposed to blood to the kidneys to the gut to the liver. This is called the diving seal reflex because it was first kind of recognized in seals which are a type of mammals. When they dive underwater for a long period of time then their blood is shunted away from the less vital organs. So you can imagine in any HIE baby if you've already had damage to the brain then you can also expect some level of damage to the kidneys to the gut to the liver. Now let's talk about the specific injury that's happening to the cells. So initially the cells lack oxygen. So the first thing that happens is that there is a buildup of acid in the cells and this can then affect the transport of ions inside and out of the cells which generally initially leads to cellular edema. So the cells just get very swollen. But what's interesting about the injury to the brain is it's just not the acute lack of oxygen that happened in that few minutes or the half an hour during delivery that causes injury to the brain. But what happens when oxygenated blood starts rushing back to the brain after that initial injury is over? This is called reperfusion injury and it's very similar to what happens in adults after they suffer a heart attack. So they have the initial injury and then the blood starts rushing back to the brain and in addition to all the acidity that there already is in those cells all these excitatory pathways are set up and the cells start going crazy. As a result of all these stimulated pathways there is injury to the brain from inflammation, from oxidative stress as well as from apoptosis. Apoptosis is a type of programmed cell death that happens when the cell decides that it should probably just commit suicide rather than bring the whole brain down with it. This whole stage, this kind of reperfusion injury stage happens within the first 6 to 12 hours after the injury and it's called the latent phase. And this really determines just how bad the injury is going to be and how well the baby is going to recover. This is also the stage that we're trying to make the biggest difference in by doing the treatment or hypothermic therapy. In the secondary phase that starts kind of after the latent phase all those processes have reached such a high point that the cells themselves actually die and there's even more injury that happens. This kind of secondary phase is normally when seizures start so really after kind of 6 to 12 hours of life. So in all these trials and studies that are being done to try to prevent further neurological damage from HIE a lot of investigators have researched trying to intervene in that latent phase to see what they could do to try to prevent more damage from being done and the secondary phase actually happening where the cells themselves actually die. Okay, I hope that you have a good understanding of the pathophysiology. Now let's move on to the diagnosis of HIE or how do we diagnose it using the physical exam as well as blood gases. So like everything else in medicine we diagnose HIE with a combination of the history with a physical exam and with lab tests. So in this case it's important not just to make the diagnosis of HIE but we also need to diagnose the severity of HIE which I'll talk about in a bit because we also need to know whether the infant is a candidate for the cooling therapy or not. So first of all we need a good history and for the diagnosis of HIE to be made then you would expect a central event to have occurred in the delivery room or right before delivery. Significant antepartum risk factors could include a very abnormal fetal heart tracing so there was significant bradycardia or maybe the OB team lost heart tones altogether so literally the baby the fetus had no more heart rate. These would all be very consistent with leading up to a significant event. Other events that we commonly see in kind of the setting of HIE could be a uterine rupture or an abruption or even a really bad shoulder dystocia where the head comes out and the rest of the body gets stuck. All of these could suggest that the baby was lacking severe amounts of oxygen or blood. As a continuation of history and also a bit of physical exam these are babies that you would expect to come out extremely depressed. So HIE babies are not born kicking and screaming and then they get worse. They come out very depressed and very often needing aggressive resuscitation. In many hospital protocols two markers are used kind of as a proxy for how much resuscitation the infant needed. The first one is having an APGAR of five or less at 10 minutes of life. Obviously this would mean that the baby is still needing resuscitation because he's not breathing enough or he's hardly got any tone. And the second one is actually needing active resuscitation at 10 minutes. So the infant at 10 minutes needs positive pressure ventilation or cardiac compressions or cardiac meds. So both of those are a proxy for having a very depressed perinatal core. Before I go over the physical exam I'm going to talk about pertinent lab values. And really when we say lab values we really mean blood gases. So the two most important blood gases that you kind of need to make a decision about whether the baby needs cooling or not are the cord blood gas and a blood gas from the baby within the first hour of life. Ideally you want both of them to be the arterial samples. So the arterial cord gas as well as an arterial blood gas sample from the baby as these will most accurately reflect the baby's current status. So quick biology lesson. If cells in our body lack oxygen then they start metabolizing anaerobically and a byproduct of anaerobic metabolism is a buildup of acid. So remember just like if you go sprinting and your muscle cells run out of oxygen they will start building up acid. So that is why you kind of cramp when you're sprinting. So we can measure the amount of acidity in blood and use it to determine how severe the lack of oxygen was. So obviously the more acidity that there is in blood the more we're worried about that the baby lacked oxygen for a longer period of time. So when we're trying to determine whether a baby needs cooling or not we look at two numbers on the arterial blood gas samples. Both at the cord as well as the baby sample. The first one is the pH which obviously the lower the pH the more acidotic the baby is the more concerning that is. The second number we look at is the base deficit. The base deficit is a calculated number on the blood gas sample and basically what it's telling you is how much base or basically alkali needs to be added to the sample to get it to a pH of 7.4. The more negative a base is the more acidotic or the more metabolic acidosis there is and the more concerning it is. So the two numbers that we use on the blood gas when we're evaluating whether an infant needs cooling or not is number one a pH of less than 7. So in the arterial blood gas sample or in the cord gas. So a pH of 6.96 or 6.85 obviously is very concerning. The second number is a base deficit of more than negative 16 millimoles per liter. So a base of minus 18 or minus 22. These babies with these gases would be considered candidates for cooling. As we discussed earlier in the pathophysiology if the brain is affected then pretty much every organ is also going to be affected. So you would expect the kidney to be affected. You'd expect a rise in the creatinine. You'd also expect the LFTs or the liver function test to go up. So elevated AST and ALT. You'd expect the overall hematological system to be affected. So you'd expect PT and PTT to be elevated. However, we don't really use these as soon as the baby is born as a diagnosis and as a way to determine whether a baby needs cooling or not because that decision has to be made almost immediately or really as quickly as possible. And some of those numbers can take a few hours or even a couple of days to really kind of reach their highest point. Okay, so now that we've talked about both the history as well as the lab tests let's talk about the physical exam. And really the physical exam is probably the most important aspect of determining how bad of a hit the baby took because it's actually the physical exam that will let us know whether a baby is a candidate for cooling or not. We use the neurological exam to diagnose the severity of HIE. So no matter the history, no matter the lab test it's the way that the baby is acting on exam that will let us know if the baby has mild, moderate or severe HIE. So at this point, I'm going to ask you to go back and look at the how to do a neurological exam video just so that you get kind of like a basic idea of what you should be doing. Now let's talk about the neurological exam as it pertains to HIE. So in 1976, Dr. Sanat, a man and a woman I don't know if they're married or if they're brother and sister but anyway there were two of them first described and discussed three different stages of HIE. They called them stage 1, 2, 3 but they correlate pretty closely to what we now called mild, moderate and severe HIE and we still use the Sanat scaling. So stage 1 was basically characterized by hyper alertness so a lot of sympathetic effects going on, high heart rate and baby just has a very active moro and active reflexes and is hyper alert. In stage 1, the baby would have a normal EEG. In stage 2, they described the babies as having obtundation so just kind of sleepiness, some hypotonia and having seizures on the EEG or even clinically. And in stage 3, which were basically the worst cases of HIE the babies were completely flaccid, barely having any autonomic reflexes so no spontaneous breathing, none of the reflexes intact just kind of lying there stuporous. So in later studies, these stages were pretty much adapted to describe which infants have mild, moderate or severe HIE and in most of the studies, it was shown that it was the moderate and the severe HIE that really benefited from the cooling therapy. So now where we stand today, we're pretty much only cooling babies that have been diagnosed to have moderate or severe HIE. There are ongoing studies to see whether cooling could still help in mild HIE but the jury is still out. So because it is so important for you all to understand the different stages of HIE I'm going to go through kind of each grade or stage or mild, moderate, severe in more detail. So in grade stage 1, mild HIE, the baby would be if anything hyper alert. So the pupils would be reactive and if anything dilated the baby's reflexes would all be intact. If anything, they would be exaggerated. So the baby would have an exaggerated moreau or exaggerated deep tendon reflexes. So again, in mild HIE, that isn't necessarily a baby that would need cooling because on exam, it is mild HIE. In moderate HIE or stage 2 where the infant took a bigger hit you would expect the tone of the baby to be decreased. So the baby would be hypertonic. The infant's pupils would be small but reactive. The respiratory rate might involve some periodic breathing. So occasionally the baby kind of forgets to take a breath or there's longer periods of time between each breath and the heart rate would be on the lower side as opposed to the higher side like in the mild HIE. A suck and a moreau are generally going to be present but they are going to be probably a lot weaker. So again, get used to examining babies, checking their reflexes their suck and their gag and their grasp and their moreau so that you have an idea of what is abnormal. If a baby has a seizure, by definition they have stage 2 or moderate HIE and above. If you're having seizures, you cannot be called or considered mild HIE any longer. In severe HIE or stage 3, then the babies are pretty much completely out. They are completely flaccid. The pupils may be fixed and dilated. Their heart rate may be extremely low. They may not have any breathing at all like making no respiratory effort and they may completely lack all reflexes. So you can't get a gag or a suck or a grasp or anything at all. Obviously, this is the most severe case of HIE. Okay, that was a lot of information today. I hope you really do understand the pathophysiology as well as the diagnosis of HIE because if you get all of that, then the whole cooling lecture is just going to make a lot of sense. So if you do have any specific questions, then please ask below. Otherwise, remember to like and subscribe and mention other topics you'd like me to talk about. Thank you so much.