Mucopolysaccharidoses & Alpha-mannosidosis: ENT & Anaesthesiology

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Introduction (Prof. Mehmet Umut Akyol)

Prof. Mehmet Umut Akyol: Okay, good afternoon ladies and gentlemen, distinguished colleagues, and or good morning or good evening depending on wherever you are in our little globe at the moment. My name is Dr. Umut Akyol and I am at Ankara, the capital of my country Turkey at the moment. It's 3 p.m. here, that's why I'm saying good afternoon, and I would like to begin with thanking all these institutions that are giving us the chance to be talking about this very important topic today.

And we will be talking about MPS, lipopolysaccharidosis and alpha-mannosidosis and the challenges in disease management from the point of view of an otolaryngologist. I'm an ear, nose and throat surgeon, I'm an... an anesthesiologist, Dr. Matthias Schäfer will be talking about anesthesiology, and I'll be beginning first, and please do not take any screenshots, do not use any slides without express written permission. Everything will take about 40 minutes, so it will be two talks about 15 minutes each.

After the second talk we will have some time for questions and answers, and we would love to hear your questions. Please submit your questions at any point via the questions panel. You can only text them, you can only write them, you cannot send them verbally unfortunately, and of course the signal will be available in this address here and you will be very welcome to take a look later.

So I am an otolaryngologist, I am an ear, nose and throat surgeon, and MPS and alpha-mannosidosis are very important subjects for me, mainly because of two or three reasons that I'll be talking about and hopefully give you a couple of take-home messages after my talk.

And I'm an ear, nose and throat surgeon, but I'm a pediatric ear, nose and throat surgeon, and as you can imagine most of my patients begin crying when they see me, but some of them are very fond of me also, and this is my best ever business card, it's done by an 80-year-old lady patient of mine who sees me as a five-star doctor, and that's why it applies to be a pediatric EMT, I like it. And what am I doing here, a pediatric ear, nose and throat surgeon, talking about a metabolic disease?

This is not my specialty at all, but yeah, metabolic diseases, especially mucopolysaccharidoses and alpha-mannosidosis, patients are very important for us. And let's see that we are talking about MPS and alpha- malonyl doses, they are metabolic disorders and they are caused by the absence or malfunctions of some lysosomal enzymes that breaks the mucopolysaccharides, in this case glycosomal glycats. We're not talking about, we're not saying mucopolysaccharides anymore, we are saying glycosomal glycats, but this is still mucopolysaccharidoses.

Why ENT sees these children: airway and infections

Anyhow, this is a genetic disorder and more than 40 of them are present at the moment, and the pathophysiology is the glycosaminoglygan that cannot be broken down by the... body, in the tissue, and that causes of course some problems. And regarding EMT, these problems are because of GAGs, the glycosaminoglygan accumulate around the ear, nose and throat area. When they accumulate around the station tube or the adenine tissue or the ear, they cause some problems, serious problems regarding hearing and hearing loss.

Of course this is an indication for us for surgery, and when they accumulate around the adenotonic ciliary tissue, the pharynx, they enlarge the adenotonic system and cause some obstruction, and that can cause some sleep problems and obstructive sleep apnea, and this is another indication for us for tonsillectomy or adenotectomy.

Not only in of course the adenotonic ciliary area, but the GAGs accumulate in the tongue causing macroglossia around the jaws and causing some temporomandibular joint dysfunction, not only in the pharynx area, but also around larynx and the lower respiratory tract, and they cause some serious airway problems that may need surgery as well, and this is a tricky area as we will see. So these are the patients who have very frequent attacks of acute otitis media, they have fluid in the ear, otitis media with diffusion,

These are the patients who have adenotonsillitis, frequent attacks of upper respiratory tract infection, and as you can see, adenoids obstructing the airway and causing some snoring, sleep disorder, and obstructive sleep apnea, etc.

This is my personal data from my own clinic, and as you see, almost all of my patients have some ear, nose, and problems, two-thirds of them have hearing problems, almost half of them have voice disorders, and one-third of them have balance disorders, and most of them, almost all of them have some edema, and the accumulation of GH is kind of obstructing the upper respiratory tract and the airway.

The important part is the diagnosis, of course, but not the diagnosis. The important part for us, for ear, nose, and throat surgeons, is the early diagnosis and of course the treatment, and if we can achieve the patient, the control of the diseases and the manifestations with minimum complications, and this is another very important part. As I said, early diagnosis is very important. It really is.

We have to diagnose these kids as early as possible in their lifespan so that they can live longer, healthier lives, a much better quality of life, of course not for only themselves but for their families and for the society too. So if we can catch them as early as possible, it will be more and more beneficial for them. We know that these patients have a different look. The physical appearance is quite different but not, unfortunately, when they were little, little babies.

By the time, the distinctive courses in their facial features, the prominent forehead, as you can see here, and an enlarged tongue with a nose, flattened bridge, and this becomes a little bit more, when they grow up, apparent. They also look alike, most of them. Some of the patients tell me that from the very early beginning, where when they were little, little babies, they had some different look.

They were not like their mother, they were not like their father or siblings, but we, as a physician, we may not really notice that.

These symptoms are not apparent in the very early babyhood. That's a very important part, and this is important because these patients, almost all of them, as you can see here, have some problems with head and neck and ear, nose,... and otitis media. They are the kids who have, you know, otitis media every other month. When they were one year of old, you had to prescribe antibiotics, you had to put some ventilation tubes for otitis media diffusion or nasal obstruction.

This is important because the mean diagnosis, at least in Europe, is about three and a half, three years of age, but we see... otitis media, upper respiratory tract infection. So we have to keep in our mind that these patients with coming to ENT surgeons, to pediatric ENT surgeons, with these problems, but also have some hernia, abdominal hernia, internal hernia, whatever, or a history of hernia-... otitis media, surgery for ENT, please keep in your mind that this can be an MPS patient. This togetherness is very important.

Red flags and the case for early surgery

Frequent attacks of upper respiratory tract, ear, nose, and throat infections, plus hernia. This leads us to MPS. So we have to keep this in our mind and tell everybody, all our colleagues, about this togetherness is very important. That's why ENTs So when we see these kids, of course we follow these kids and we do our ENT examination as usual, but our most important tool here is flexible endoscopy.

As you can see here, my flexible endoscope, this is an enlarged adenine tissue, this is edematous tissue, you see a little bit whitened because of the obstruction, and of course laryngeal area, you see that there's edema, there's GHs accumulate and causing kind of an obstruction, and this also is true for the vocal cords.

Although it is two or three years... a voice of a rock singer smoking three packs a day, and that's because of the accumulation of the GHs in the larynx, and this is the ear, as you can see, the membrane is dull, white, and it's a little bit retracted, and this shows that fluid in the ear. This is also very important because this fluid in the ear causes some hearing problems and hearing is very important for them, for their treatment, for their growth, so we have to keep the hearing in the best position we can.

They also have pediatric obstructive sleep apnea syndrome, most of them because of the obstruction of the GAGs obstructing the upper respiratory airway, and all these need some surgery, these are indications for a surgery, and this is the second tricky part. Here I have to unfortunately talk about a I will give a brief information.

That was a 10-year-old female MPS patient with unfortunately very, the disease is very, very bad and had been under the treatment for years, not treating unfortunately, but that was a very advanced disease where the morphological changes took place, the spine, the ear, nose, and throat, head and neck area, serious cranial, facial, and vertebral complications, and also had critical obstructive sleep apnea syndrome.

So we have to do something about that, and one of our colleagues tried to do an adenoselectomy in this kid, but she was refused by a senior anesthesiologist at the time since it was very, very dangerous and rescheduled.

decisions followed each other. The kid got worse and worse, cannot sleep and cannot breathe. So one of our chief residents took her in the operating room a couple of months later. They had to open a tracheotomy in order to make her breathe and do the DNA surgery but as expected all the complications followed each other. The respiratory tract was horrible and the pulmonary function was very, very low. So unfortunately we lost this patient of us post-operative second day. So that made us think more and more about MPS patients.

As you can see in some patients you cannot really extend or flex the neck in order, even open a tracheotomy is not possible in these kids. You cannot put them in supine position and doing surgery in these kids is very, very, very dangerous. These are the kids who have all kinds of complications and the airways also, as you can see here, the trachea is very important... unfortunate. So there is a dilemma here.

We are in a position that we have some kids here that need surgery and we have to do surgery because they have to hear, they have to sleep and they have to grow up and we need to help them. These are the kids who have when we have to operate as soon as possible. But on the other hand we know that these are the kids who have really high morbidity and mortality, the pre-operative, post-operative period. So most of our colleagues do not want to operate them of course.

We talked a little bit about that and we talked between ourselves and at least in my opinion this solution at the moment is the indication and the timing of surgery is very, very important. Whenever you have to treat these kids surgically, do it as soon as possible. Before the morphological changes happens in their body and the airway becomes very, very dangerous to get into an operation.

So do not wait. Do the operation as soon as possible before it is too late and do the operation in a setting with a multidisciplinary team. This is very important.

You have to get a very good anesthesiologist, you have to have some ICU people, pulmonologists and you have to decide together of course with your metabolic disorder specialist and of course the family telling them the dangers about the operation. So the two main points regarding ENT. We can diagnose these kids as early as possible, keeping in our mind that they... sclerotitis very frequently, plus hernia very early in their lives. And the second thing is treatment can be tricky.

Please treat these kids in a setting in a multidisciplinary, big tertiary centre and if you have to do a surgery, do it as soon as possible. This was my point and thank you very much for listening to me. Now I am very, very proud to present my colleague Dr. Matthias Schaefer from Germany. Dr. Schaefer, it's your turn now.

Anaesthetic risks in MPS and alpha-mannosidosis

Thank you very much for your kind introduction and opportunity to follow the ENT session with problems of anesthesiology. Of course we have in patients a lot of problems if they will be operated, they need almost anesthesia and it's good to have an overview of the current problems and the procedures or the management that you can overhaul many of the problems that can occur in those patients. They will be operated for many reasons from small ENT surgery up to cardiac surgery.

There are various operations and diagnostic procedures in those patients where the anesthesiologist has to deal with. And as Umut stated before, it's almost crucial that you have a careful pre-anesthetic workup in an interdisciplinary team, talk to the surgeons, the pediatricians, the intensive care people and gain as much information about the patient, about his... cardiovascular situation and others. And look for the cardiovascular system, plan the rescue maneuvers and plan the post-operative care with this team.

Well, many of the risk factors connected to this progressive disease is more or less not the enzymatic problem but the somatic impairment of the patient, the deformed chest, recurrent infections, restrictive or obstructive ventilation disorders and tracheomalacia.

And also the cardiovascular system is involved.

in some patients also the cognitive impairment. The most of the anesthesia risk is dealing with the airway because of the already shown the GAG deposits in the tongue and the soft tissues of the oropharynx and the trachea. So we have a high rigid and thickened epiglottis, tracheal obstruction, tracheomalacia, macrotrachea, the ankylosis of the temporal mandibular joint and a reduced cervical spine mobility. And in multiple patients, there's added the instability of the atlantoaxial joint.

These are all problems that make intubation and airway management very difficult for anesthesiologists and therefore you have the almost difficult intubation conditions. As in the literature reported, among the different types of MPS, you have the different incidents of airway problems or intubation problems up to 100% in MPS4 and around 50% in airway. Well, how to deal with that problem as an anesthesiologist?

We have a proper workup of the airway, the quite normal clinical grading of the Mallampati score, and we do often an endoscopy to clear up where the lower airway is obstructed or deviated. And as you can easily see, the trachea may be obstructed or the trachea may deviate and almost diff problems in the atlantoaxial joint. So as you can see here, we see the, sorry, as you can see the obstructed trachea, the almost clumsy introitus of the larynx and you have high difficult intubation as you can imagine.

Beside the problems of the airway, we have also the cardiovascular system involved in those patients. Most of them have other diseases, like mormor, cardiomyopathy, and other cardiovascular symptoms. Most of the abnormalities deal with the left heart and more or less the mitral is more than the aortic valve involved and drug agitation is more common than stenosis. Additionally, you have left ventricular dilation, hypertrophy, diastolic and systolic dysfunction. And you can see here a section of the heart.

It's a very thick ventricle, which leads to cardiomyopathy and the subsequent problems in oxygen, supply and demand ratio of the heart. And more or less, you can find in those patients, let's say, coronary artery disease-like status because of gag deposits in the coronary arteries and the inflammatory triggered intramural proliferation. So it's more or less the same consequence as you find in severe cardiac coronary vessel disease.

Conduction abnormalities, pulmonary hypertension, these all states to increase cardiac oxygen consumption and decrease oxygen supply to the myocardium. And there is a low tolerance of red blood cell variations throughout induction and through the operation.

Dr. Schaefer, please.

Demand ratio of the heart.

Managing the airway (Dr Matthias Schäfer)

Dr. Matthias Schäfer: I'm adding information about all the stuff it can find from the patient throughout the operations. If you have the patient intubated and everything is okay, you find difficult positioning by the thoracic deviations, the prominent abdomen and joint contractures, therefore you should review all the imaging studies who are available of these patients. So managing the patient is not quite very different to what you do in a patient with severe airway obstruction.

You should do after the workup, identify the risk factors and add your experience and the equipment and decide whether you use sedation, regional anesthesia or general anesthesia and how to manage the airway during induction or positioning and the monitoring. Especially look for the rescue maneuvers that you have available if something doesn't work like plan A. You have to prepare plan B and C and D and look for the adequate equipment. You can decide whether you induct the patient in a subine, lateral or sitting position.

Sitting position or lateral position is better for opening the airway, the lung expansion and for maintaining spontaneous ventilation which is crucial if you have a very, very severe obstructed airway and so you have a lot of time to manage the airway if the patient is spontaneously breathing. Therefore more or less it's good to do an awake intubation or use inhalational induction to maintain spontaneous breathing as long as you can.

So the different ways to manage the airway are well known among the anesthesiologists, I don't want to mention so much, but you can use quite a normal laryngoscope which or LMA so let's say 50% of the patient. An LMA is sufficient to secure the airway but in the severe cases I would strongly recommend to use fiber optic devices from the nasal or oral route in an anesthetized or let's say awake or likely sedated patient. The crucial thing is to maintain spontaneous ventilation as long as you can.

The fact that you use let's say more or less in a light sedated or awake patient use local anesthetic for the airway like lidocaine and the drugs you can use among all your drugs that you have in your chart. I would recommend using very short acting drugs like remifentanil if you use opioids or propofol but you can also use Midasolam or Ketamine if you are experienced with this.

After that my experience is that the airway algorithm of the ASA doesn't work so properly so you have to be prepared in plan A, B, C, D and E so prepare all your own stuff and your staff in the way that you can go out of a critical situation easily by preparing all the things that you have ready if you have problems with managing the airway.

A regional anesthesia for peripheral surgery is a very good alternative to use, to choose because you don't need general anesthesia and we are out of the airway problem but if it doesn't work you have to secure the airway itself. It's good for upper or lower lip surgery and is recommended if applicable. Spinal and epidural it's quite a problem.

We have some case reports about successful epidural anesthesia and some case reports about successful spinal anesthesia during delivery and so on but it's still not recommended because paraplegia after epidural anesthesia in an occupation has been described and we think that gag deposits in the nerve shell leads to failure and the spinal abnormalities may affect the spinal cord perfusion. This may cause neurological problems after using this method therefore the regional anesthesia, spinal anesthesia or so on is not recommended in these patients.

So if the surgery is over, the story is not over, you should think on the emergence of the patient. The extubation strategy is so that the patient should be awake and should maintain his airway open. Then you will deblock the tube and have a contactable patient before you take out the tube and a step-by-step removal technique of the E-tube and it's a good choice to have a tube exchange available that if you are wrong by the extubation you can easily re-intubate the patient. And also the post-operative care is crucial of these patients.

You have a high incidence of laryngeal or subclotic edema with a late onset so it has been reported up to 24 hours after extubation. You have the already mentioned from Umut the abstraction of the tracheal laryngeal malacia problem and there is also described the post-operative pulmonary edema in those patients. Therefore in the recovery room CPAP therapy is very strongly recommended and you should monitor the patient for at least 24 hours, perhaps depending on his state.

the surgical procedure, it's good to leave him one night at the ICU. Tracheostomy as a way out of a difficult airway is not a good idea in those patients. It takes a lot of time, just as Umut told us. It's very difficult even for a very experienced ENT surgeon to do a tracheostomy under those conditions. So, a tracheostomy itself causes a lot of problems for the patients in the following years.

Take-home messages on anaesthesia

So, in summary, your take-home message from my talk is have the qualification of an experienced team, weigh the benefits ratio for the patients, assess the patients with cardiac neurology and ENT findings, positioning of the patient may be crucial during intubation and during the surgery. Look at the atlantoaxial joint or problems with the cervical spine and monitor the patient carefully to avoid hypertension and if the spinal problem occurs, you should use perhaps the neurophysiological monitoring on a very wide basis.

And for the anesthesia technique, think on maintenance of spontaneous ventilation as long as possible, use regional anesthesia, light sedation if applicable and don't think on epidural or intrathecal anesthesia because of their unknown effects on the disturbed spinal perfusion. So, this was my talk and I think we should go over to back to Jumant.

Prof. Mehmet Umut Akyol: But yes, thank you very much for the brilliant talk and now it is time to answer the questions. Please keep sending your questions, text your questions, we will be very happy to answer them and I'll begin to read the questions. is for me. A colleague of us is asking how should we handle a patient with MPS who already had three episodes of otitis media dysphagia.

Questions and answers

Okay, thank you very much and I told you these are the kids who So, if they had recurrent otitis... otitis media with effusion, with effusion

type large tubes... that these... I want to stay there for a longer time. I'm not using long-time standing tubes, but I will put a big large diameter tube that will take a long time and won't wait for the patient to progress and that can be more serious for anesthesiology. And let's see if we have some other patients.

Yeah, another question. A ten-year-old small-scale patient should receive anesthesia for import implantation. For this small procedure, LMA is routinely used in otherwise healthy patients. Okay, is this also advisable in more care?

Mathias, for you.

Dr. Matthias Schäfer: Thank you very much for this question. This is a very crucial question because it depends very much on the status of the patient. Morquio patients tend to have problems with the atlantoaxial joint and if you put in an LMA you know that you have to move extremely the cervical spine. Therefore, I would not recommend at itself to to use LMA as a first approach.

If you have radiographic findings that rule out any problems in the atlantoaxial joint, this might be a very good choice to use the LMA as a very non-invasive method to secure the airway.

But to be very sure, you should better intubate the patient with a fiber optic device. I experienced two cases of comparable situations: very small procedures. The anesthesiologist took an LMA and moved the head and moved the cervical spine for, quite in a normal patient, for nothing, but both patients awake with paraplegia. Therefore, I would be very careful to use LMAs in Morquio patients. Thank you.

Prof. Mehmet Umut Akyol: Next question: okay, assume for me yes for adenotoxinectomy, until which age should we wait for the operation and where should it be done? Okay, if there is an indication for adenotoxinectomy for airway surgery, I do not have any age limit. I can do it anytime, any age, any season. The very important thing is, of course I should be talking with the anesthesiologist and my team and we have to decide it all together and it's a multidisciplinary approach. So I will not be waiting any certain age like two years of age.

Two years of age: if they need surgery, I will go and do it as soon as possible before the disease progresses and some irreversible morphological changes take place. So there is no time limit for me. You can do the surgery anytime. Do you know that? Yes, let's take another question now. You can keep on sending your questions, please.

Oh, this is for dr schaefer. A nine- year- old May Hurler patient is scheduled for a small EMT procedure. It is also planned to repeat MRI in the next couple of weeks.

As far as he didn't tolerate MRI without heavy sedation during the last session, the question had been raised to combine both in one anesthesia. Is the prolongation of the anesthesia by having MRI time higher risk compared to two separate procedures? Really good questions, Dr schaefer. This is what I also experience from time to time. What do you say?

Dr. Matthias Schäfer: Thank you very much for this very, very interesting question, because this is clearly addressed to what we both said. We should discuss those patients in an interdisciplinary team and, if you have the EMT surgeon on the one side and, let's say, the orthopedic surgeon on the other side who wants the MRI scan. We have to talk together what is the best way for the patient. If the patient has intubation problems to via intubation problems, clearly induction of anesthesia.

Intubation is the main risk and therefore it's better to avoid a second intubation for an MRI or so on. If the patient is not so much somatically impaired, it might be justified to give two times anesthesia and to give two inductions and two intubations. This should be not a problem. But if the patient, like a roller patient mostly, are severely impaired, the intubation is the critical part.

Therefore you have to combine both procedures in a very easy way and the prolongation is not so much a question of a risk because if you don't move the tube so much and don't move the cervical spine so much, be careful and just to avoid the edema that can be occurred if you have stress on the trachea. If you look at this point very carefully, it would be better to combine both procedures in one anesthesia for the patient, unfortunately, thank you.

Prof. Mehmet Umut Akyol: Yes, it also depends on the institution, your institutions. You know physical appearance. You have to take the kid with ample back all the way to the radiology. You do not do not have MRI close to the operating theaters, but this is a very good question. Thank you very much for the answer and let's see if there are any other questions, and as far as I see, I cannot see any more.

Well, then it is time to say thank you very much for listening us and thank you very much for taking part in this webinar, and we hope we did able to send a couple of take-home messages with dr matthews Schaefer, and I wish you a very good afternoon and thank you again for joining us, and I would like to close this seminar.

Matias passwords, thank you very much and best greetings from Germany.

Okay, you will have a very, very good afternoon. My dear colleagues, ladies and gentlemen, this is the end of our webinar. Thank you very much.

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