Slides
Transcript
Good afternoon everybody. Thank you especially to the organization for inviting us because I and Dr. Leffert, we believe there is very much overlap between these two syndromes, at least in the initial phase.
I’m going to talk a little bit about the origins of the PDPH, and I’ll try to tell a little bit of the history because it always starts someplace. I’ll have a short personal reflection on pathophysiology. I will talk about the significance in obstetric anesthesia, but not too long because that’s what Dr. Leffert concentrated upon, and some therapeutic considerations based on the EPiMAP study in which I was involved, which studied about 600 plus epidural blood patches after PDPH in a post-delivery, which might be of interest for the audience, and some personal conclusions.
Well, we all start with August Bier, a surgeon, and he was the one who first successfully used spinal anesthesia. And actually, some people call him the father of spinal anesthesia. But I disagree, actually, because if you talk about anesthesia this way, I don’t think you deserve the term father of spinal anesthesia. I think he rather deserves the term father of PDPH, because apart from having the first eight patients who had spinal anesthesia, he experienced himself post-dural puncture headache himself as well, because together with his assistant after patient six, they started doing some experiments on themselves in the evening, and they had quite some difficult efforts to achieve spinal anesthesia, and quite some CSF was lost along the way. And they ended up with having some cigars, and they were actually very happy. They had a glass of wine, went to bed.
In the morning, he went fresh and awake. He went around, walked a little bit, but in the end of the morning, a little headache started showing up and he wasn’t really concerned about it. But during the day, the headache got worse and in the end, he ended up in bed. And as long as he stayed supine, the headache was okay. If he was up too long, it came immediately back again. And he became a little bit dizzy. He had some dizziness around. In the end, he was nine days in bed and it took him 13 days before he could go hunting again. So, the usual hobby of the medical profession at that time in Germany.
Well, according to the definitions we have heard in anesthesia, it’s a clinical diagnosis. We never do any diagnostics. If we have a story which fits the precise criteria from the international classification, we proceed and try to treat our patients. But I want to reflect a little bit on the basic underlying pathophysiology because it’s always related to the Monro-Kellie doctrine and that the static components of the brain should be always in equilibrium. So if some volume is lost in one compartment, the blood and the brain tissue have to compensate. Now there’s little place for brain tissue to compensate, so it’s probably the blood which compensates by vasodilation. But the Monro-Kellie doctrine has become a little bit more dynamic luckily, and these days it’s realized more and more that you cannot always consider the intracranial component as a closed block cabinet. There are connections with the outside world through different parts, through the venous system, through the spinal CSF system. So it’s becoming a more dynamic philosophy. What the consequences are for PDPH, I don’t know yet, but we should think on how to go onwards with all the new findings we find in the new basic science related to intracranial CSF and the rest of intracranial homeostasis.
I want to show you a picture of not really a patient story. This was an experiment 20 years ago done by a South African doctor where he retracted some CSF in the basal cistern of anesthetized pigs. And what he saw the moment he started getting volume of CSF out, he saw the cerebral blood flow going up, which is quite understandable because if you look at Monro-Kellie, you get one thing out, okay, the other thing has to become extra, so there should be more blood. And he found the very strange other finding, which I still don’t have an explanation for. If the tap he did in the basal cistern was a little bit bloody, he didn’t find the increase of the cerebral blood flow. So there was something different suddenly not being compensated. I don’t know.
But this is basically for me related to the cerebral blood flow autoregulation partly. But autoregulation, the components of the autoregulation, we don’t know them all. We know that there is, of course, immediate response to changes in the cerebral perfusion pressure, but there are also local responses to all sorts of substances, to hypocapnia, to hypercapnia. And we shouldn’t forget the innervation of the autonomic nervous system. What does the autonomic nervous system do to the cerebral blood flow regulation? Are we interested in it as clinicians? Not really, but maybe we should. And then of course there are fibers of the trigemino-neurovascular system.
And what about glymphatics? I am always wondering what is CSF? Where is CSF? How far does CSF go? Where’s interstitial fluids? Well, luckily many people are wondering this as well, and there’s a whole new science developing where there are ways being discovered how CSF reaches the interstitial fluids, and it’s quite, it’s very interesting material. You should all dive into it. But to me, it didn’t solve my initial impression because as far as I’m concerned, and I’m very, I’m a simplistic anesthesiologist, but I believe CSF is nothing more than interstitial fluid. And I always say the brain is a sponge floating in a swimming pool. But it takes a lot of research before we are all going to have a final statement of what is CSF in the end and what is the consequence for PDPH? What is the consequence if you have a leak somewhere and you lose CSF? How is it replenished? Is it suddenly that all the interstitial fluid disappears as well? These sorts of mechanics are not being looked upon, and we should look upon them.
I compared with the Dutch national landscapes, at least in Holland. I’m not from Holland, I’m from the southern part of the Netherlands. But if you see the canals which bring water, which take away the water from the lower laying parts, it’s a continuum. So the fluid which is coming to each and every individual little tree you can see or any house you can see, it’s the same water which is going in the canals outside, but the consistency changes. So it’s not a matter of different substances. It’s a matter of different solutes and local changes, but in the end, it’s still the same water.
But going back to my story, PDPH and obstetrics, it’s serious. We have heard it has chronic consequences in a time and moment very important for all of us. The beginning of a new family. And anesthesia, it’s not spontaneous — we are because it’s an iatrogenic thing. So we feel responsible for it, and it affects maternal well-being and the family well-being, and it’s not always self-limiting. The consequences can be serious. So we have to treat it.
We have to treat it adequately, and that’s why this guideline was made by this multisociety working group. Dr. Kranz was part of it. Dr. Leffert was part of it. But the evidence was very, very thin, and these were actually the only treatment options which had any substantial support of evidence. And you can see regular multimodal analgesia. Well, who can be against that, more or less? What to do when there are serious neurological deficits? And of course, when the PDPH is serious, we move to a blood patch. And this brings me, of course, to Dr. Wouter, because in the end what we do as anesthesiologists, the same as Dr. Wouter, we plug the hole. We do it in a different way, but somehow we are related in this topic.
This brings me to the EPiMAP study. And Anil Gupta, the guy you see right up there, was a professor from Uppsala, Sweden, anesthesiologist, and he was curious as well as I. Why are blood patches failing? But how do you collect enough patients? Because we all have a patient here, a patient there, the same problem. You have a spontaneous intracranial hypotension. So we set up a multinational, international cohort study. Many European countries contributed, and in the end we had 1,001 patients of women who had a PDPH after an accidental dural puncture. And we found, of course, what everybody else found, accompanying SIH syndrome symptoms. I left out neck pain, but indeed it was there as well. The interesting finding was actually that we only included patients where we had an accidental dural puncture visualized, experienced by CSF aspirating from the catheter or spinal anesthesia after giving a test dose, or if there was only PDPH afterwards. If you look at the percentages, it’s more than 100% because some patients had double answers.
But in the end, 30% of PDPH was not recognized, and not recognized actually — these women had adequate analgesia through an epidural catheter, and they didn’t have any symptoms that any of that material would be leaking into the intrathecal space. So a very uneventful epidural.
Now what were the findings we had? Of course, we were interested in which women are the ones who get an epidural blood patch. And as you can see, the light-colored ones are the patients who are treated with conventional therapy. And you could see that once the PDPH was diagnosed, the women who had less headache in the next measurement, and even less afterwards, they were the ones who were not getting a blood patch. If the pain increased during time after diagnosis, most women received an epidural blood patch.
Now, which factors were associated with conservative management and epidural blood patch? I’ll call them out very shortly. They’re not of very practical interest because this was a cohort study. It was a multinational project. It is very much confounding in here, but it was an interesting finding. It was an epidural at level L2-L3 compared to a lower level of an epidural accidental dural puncture was related to epidural blood patches. We could definitely not explain it, so we ignored it more or less completely.
And then there was, of course, the use of air for loss of resistance, which was associated with conservative management, which was interesting as well from a specific part of the way I look at it. And the use of intrathecal catheter, once you were epidurally and you inserted the epidural catheter intrathecally, it was associated with conservative management instead of needing an epidural blood patch.
Now the second study we made from the EPiMAP project was where we looked into factors associated to failure of the blood patch. In the end we had 643 epidural blood patches from these thousand patients and these were the factors we considered relevant to failed epidural blood patch: patient-related factors, epidural-related factors, headache-related factors, and especially factors related to the epidural blood patch itself. And we were discussing how are we defining a failed epidural blood patch. So we said initially, well, if you have an NRS score higher than three we consider it a failure, or if you need a second blood patch. But some colleagues said rightfully, what happens if you had an NRS score of nine initially and it lowered to four? That could be called a success actually. So in the end we had three categories. We had failure, partial success, success. And as you can see, a real failure was if you had an NRS score higher than seven after the blood patch or you needed a second blood patch. So what came out eventually, only 33% of our epidural blood patches were completely successful and 28% of the blood patches completely failed, and then there were 38% in between who had partial reduction of their symptoms.
Now which factors were associated? These were the three which came out significantly. Since this was a cohort study, I don’t have a pointer, but if you look up in the upper right corner, we chose for a p value of 0.01 because it was a cohort study. There would be a lot of confounding and we didn’t want to get a lot of findings which we couldn’t explain anyway. Well, these findings we couldn’t explain them all either. We found that women with a previous history of migraine had a higher risk of a failed epidural blood patch. We also found here comes again the level of the accidental dural puncture which originally initiated the PDPH was related to increased failure rates but also to increased only partial success rates. And then the third finding it did matter if you gave a blood patch later it was more successful, but this was a known finding which we had expected to find anyway. But we had thought what if we would have taken the p value of 0.05. Would we have found anything else? Well, okay. A bigger needle, less experience of the provider originally. Curious finding. First mobilization after an epidural blood patch. If you mobilized late after a blood patch, there would be a risk of having a failed blood patch. This is an interesting finding as well, which we cannot explain, but it should make us think. But all the things we had thought about which we thought were relevant, volume, level, experience, position during the epidural blood patch, they didn’t really come out. So it didn’t bring us much further.
The volume issue was difficult to have it demonstrated any effect because most women received about 18 to 20 mL because of this previous study done in obstetric anesthesia. Going back a little bit into the migraine story, we were curious why do women who have migraine have a higher risk of a failed epidural blood patch and a higher risk of maybe more severe PDPH. If you look at the table, actually they didn’t have more headache after the blood patch than the women who didn’t have migraine, but they had more often a second blood patch. So in the end we think that women who had migraine were more prone to not accepting having wanting to go home and go for any therapy as long as they could go home and maybe the doctor same story to make a distinction between migraine and PDPH I don’t know, but this is the only reason. The level story is actually quite interesting for me as an anesthesiologist. Why does a woman who has an accidental dural puncture at the higher lumbar level compared to a lower lumbar level, why should she have a failed epidural blood patch more often? We saw already that they had an epidural blood patch anyway more often. But what is the association? We didn’t know. We didn’t understand. So we said, well, anesthesiologists, we are very bad in determining the level. So it’s a strange confounding thing. But if we would have had a monkey determining a level at random then we still shouldn’t have seen any difference. So the fact that we found a difference actually is demonstrating that we weren’t so bad in our level determination.
But if you look over here, these women had—indeed they had—more severe headache if they had the original epidural accidental dural puncture at several, both immediately and longer after. At 48 hours after, the effect was not really significant anymore. But we had been talking about the level of the blood patch, which in itself was not a risk factor for failure. So we connected the two, and we said is a relationship between the level of accidental dural puncture and the epidural blood patch itself? And the only thing what you can see, it’s not the level of the epidural blood patch. So if you do them at the same level, it doesn’t—if the epidural blood patch is lower than the accidental dural puncture, that means that the accidental dural puncture is high—then you see that the risk of failure is… no, I say the other way around, anyway, it’s the level of the accidental dural puncture which is determining if a blood patch fails or not. So even if you have a low epidural accidental dural puncture an a low blood patch, it’s not related to failure. The moment the epidural accidental dural puncture is higher, that’s where the relationship shows significant differences in failure and success.
But blood patches are an invasive technique. We’re not so happy about it, so we go for conventional methods. We look to drugs. We look to simple invasive measures aimed at various philosophies of the cause of PDPH, many of them focusing on cerebral vasoconstriction. And Dr. Leffert called already some of them out, and I’ll give a little bit more detail about this sphenopalatine ganglion block. She showed already how it was done, and it was popular in the beginning of the 20th century because of cluster headache. But unfortunately they used cocaine, so all these doctors who used the sphenopalatine ganglion block, some of them couldn’t resist the addiction, and that was one of the reasons the sphenopalatine block was forgotten.
But it’s back into the interest again, and you wanted some data. Well, there is a study group from New Jersey. They’re very keen on this sphenopalatine ganglion block and they looked at about 81 cases that had PDPH. Some of them were treated with this sphenopalatine ganglion block, some treated with an epidural blood patch. And as you can see, the success of the epidural blood patch itself is bigger. 87% is successful after one attempt compared to about 57% after one or two sphenopalatine ganglion blocks. But at least it does something, and we don’t know precisely what. As Dr. Leffert says, the ganglion is not very easily accessible. So if we put some cotton swabs in the nose, are we sure our drugs definitely to the place they have to be, or do we have to do a more invasive transcutaneous approach, or should we have some stimulation? I don’t know.
This is an interesting study in that regard from Denmark, where they had 40 patients where they randomized the sphenopalatine ganglion block with saline compared to local anesthetics, and the surprising finding was that actually the saline worked as well. Is it only placebo? Is it only placebo effect and nothing else? Or is the fact that you poke around with a little cotton swipe in the back of your nose triggering a sort of reflex mechanism which affects pain? I don’t know. That’s definitely one of the topics we should go and research a little bit more in the future. In the meantime, we should do something about the definition because even PDPH, which is category 7.21, says we should fulfill criteria of 7.2. But the thing is we never do any diagnostics to begin with.
Secondly, it’s not a dural puncture. It should be an arachnoid puncture as well. So the definition of post-dural puncture headache, the name of post-dural puncture headache, it’s maybe still not the optimal name, but we’re never going to change it. So we’re stuck with it. And lastly, we have seen the symptoms are not always disappearing. They can become chronic and they can appear later than 5 days after dural puncture. And of course the fact that they left out the positional component makes sense in one regard, but on the other side it’s one of the most important things in which you recognize there is a problem. So as far as I’m concerned, you rather make a note that it’s not always true, but you should get a positional [inaudible] on it.
What is the cause of PDPH? Is it just loss of CSF through the leak? And does it cause traction, vasodilation, or activation? Or as far as I’m concerned, PDPH is a result from disruption of the normal homeostasis. And I don’t know, at least in anesthetic PDPH, if this leak has to be persistent, and I don’t know actually if this vasodilation if it’s secondary or if it’s caused by other mechanisms we don’t know. And we should go back to basic science because we don’t have answers for many questions. I’ve heard here for one day, for one and a half days, you don’t have answers for some specific things, and we always tend to ignore the things we cannot look into. But there are a lot of new tools and a lot of new basic scientific methods we should start looking in again. And we should go back to the basic presumptions we make and take for granted, which actually are not always for granted. That’s the only way to answer all these questions. Why doesn’t an epidural blood patch work? Well, actually, why does an epidural blood patch work?
The bloody tab story, the patient-related factors, why do skull-based CSF leaks, why don’t they cause meningeal enhancement completely? I don’t know. It’s a lot of questions.
My conclusion is the definition is inadequate. The pathophysiology is much more complex. Our treatment responses are completely unpredictable, and we have individual variations. So we have a lot of work to do, and not only these people. We have to get basic scientists in here, because altogether we can really look anew, and we don’t have to find our research on presumptions made 40, 50, 60, 80 years ago. We have to do together, make a new effort to go back to basics as well.
I’ll end with my dear Dr. Professor Bier, and I agree with him in this regard. A professor is somebody with a different point of view, and many different points of view, which are hopefully here in the audience, will make solutions for many problems related to CSF leaks. Thank you.