Laura Glaganski, MD & Jagroop (Rupi) Parikh - 2024 Fetal Care Center Navigating Perinatal Care for Trisomy 13 & 18

All right. Uh, so next we'll be talking about the, uh, practical considerations, um, for surgical patients. Um, and I'm joined, uh, by one of our anesthesiologists, uh, Doctor Ruby Pree, who'll be talking about, uh, the anesthesia perspective as well. Um, but I'll start with the surgical perspective first. Uh, we're gonna talk a little bit about, uh, common surgical needs. For patients with trisomy 13 and 18. Uh, we'll talk about risk factors associated with mortality after surgery, um, key airway findings in these patients, uh, as well as touch briefly on surgery for hepatoblastoma. Um, and then we'll talk about anesthetic considerations. Uh, as many of you may know, uh, the various anomalies, uh that these patients have, uh, all can potentially require a procedure or intervention, uh, ranges from, uh, neurologic anomalies, um, ear, nose, and throat anomalies, uh, challenges with the airway and, uh, dynamic airway changes, uh, genitourinary and gastrointestinal anomalies. Um, many patients will require, uh, surgical feeding access, um, as well as, uh, musculoskeletal challenges, um, that could need intervention and, um, issues with, um, their eyes. Um, as Doctor Schwarz started our session off, um, talking about the study, um, out of Ontario, this one, I think helped a lot in terms of identifying, uh, long-term surgical needs for patients with trisomy 13 and 18. Um, as we discussed, this is a longitudinal population study. Um, and it was great to take essentially all comers, uh, with these diagnoses to identify who was, uh, getting surgery. And for patients with trisomy 13, um, that was 23% of patients, and for trisomy 18, that was 18% of patients. And when we look at uh those procedures in a little bit more detail, um, this is the gastrointestinal, gastro or excuse me, genitourinary uh procedures as well as uh ENT. Um, the procedures are divided up, uh, on the Uh, columns as major and intermediate, those are those requiring um inpatient hospitalization, whereas the minor procedures are those that are just outpatient procedures. So with the associated, uh, comorbidities and anomalies with Rome 13 and 18, um, there's a pretty wide range of procedures that could be needed for a given patient. Um, and that extends into the pulmonary, uh, neurologic and musculoskeletal, uh, side as well. Um, this, uh, does not have listed minor procedures just because based on the number of patients, um, they were included for privacy reasons. Uh, but most Commonly here um under the technology, um, portion is that where a feeding access is, uh, commonly used. So many of the patients had either a gastrostomy tube or Jinnostomy tube placed to help with feeding. And when we looked in more detail for these, Sorry, my slides are struggling to advance. Um, we found for choosomy 13 here that 41 children, uh, underwent 135 surgical procedures. So right off the bat, we know that, uh, there's a higher number of, uh, procedures per patient, um, than just one, like one patient just needing one procedure. Many children are going to need more than one, for a given, um, Anomaly or challenge. Um, of the people, of the children undergoing surgery, um, 16 of them, which was 39% with trisomy 13, had one lifetime procedure, but 15 of those children had 4 or more lifetime procedures. When compared with trisomy 1835 children underwent 92 surgical procedures. And if you look at the age of the procedure like we briefly talked about before, uh, many of these procedures are happening within the first few months of life. Um, however, overall, the median survival after the first surgery was more than a year, um, in all of the organ system categories except for the eye surgeries, um, and in cardiac surgeries with trisomy 18. Now, we talked, this is a little bit of more of a historical cohort um that was uh patients from 1990 to 2012. So if we look at a little bit more, excuse me, contemporary cohorts, um, this is a study out of Indiana. This is a retrospective, uh, study, patients uh from 1990, but all the way up to uh 2020. Um, this looked at, um, Patients treated in their centers um and identified 117 patients, um. But of note, 30% of these had other chromosomal 18 variants, which would include uh trisomy 18 um mosaicism, um, and they've assessed predictors of mortality after surgery. Uh, they found that of their patients, 53% of patients underwent a procedure, so higher than that, uh, previous, uh, study had mentioned. Um, and the median age of their first procedure was 65 days. And what they identified uh as risk factors, uh, were that higher birth weight and later gestational age had a lower mortality, um, just as you heard from Doctor Sonoda, um, that that impacts the cardiac, uh, outcomes, um, that applies for all other, um, surgical procedures. And also they found that patients with other chromosome 18 variants, again including the mosaicism, had lower mortality. Um, when they looked at different types of comorbidities, the general surgical anomalies, uh, which includes the, uh, esophageal atresia, um, were associated with higher mortality. So, but in comparison, looking at neurologic procedures, ENT procedures, defects in the abdominal wall, genitourinary, um, procedures, and endocrine comorbidities, those are not actually associated with increased mortality. This is the Kalenmeyer curve, um, looking at those who had what you could call a classic trisomy, um, of 13 or 18 versus a variant, um, and they found on the bottom curve that those with, for example, mosaicism, um, had a much lower mortality of the, of those patients that were undergoing surgical procedures. Uh, next, we wanted to spend some time talking about, uh, airway findings because just as Dr. Sonoda was alluding to, um, the patients with trisomy 13 and 18 have significant, um, airway findings, um, and that can impact their ongoing care and what, uh, patients would benefit, um, and be able to tolerate going forward. So this study um is uh out of Cincinnati Children's uh looking at patients retrospectively from 2011 to 2021, um, and this identified 1331 patients, excuse me, 6 with trisomy 13 and 25 with trisomy 18, um, and again, there was a good portion of patients that had uh mosaicism in this cohort. The indications for performing a bronchoscopy, whether flexible or rigid or both, uh, for these patients was largely for sleep apnea, um, but some patients also had it for failure to extubate, um, and aspiration. The median age of the first bronchoscopy for these patients was 10 months. Um, and you can see the pictures on the right, uh, that demonstrate, uh, some of the findings that we'll talk about that they found in the patients with trisomy 13 and 18. Um, and that's Significant, uh, airway collapse at multiple different levels. Um, so the column on the left shows, uh, the patient when they inhale and, uh, at different levels of the airway, whether it's the, um, hypopharynx, the trachea, or even down into the bronchi, um, that with, um, Breathing, that you can have different levels of airway collapse, uh, which can significantly affect, uh, the patient's respiratory support needs. Um, so this is what they found when they looked at the frequency of airway findings, uh, in trisomy 13 and 18. So the green, uh, is that the patients with trisomy 13 and blue is with 18, um, and Uh, all of the patients with trisomy 13 had more than 3 significant findings on bronchoscopy. These are findings that affected both the upper and lower airways, meaning the trachea and into the bronchi, most commonly, and most patients with trisomy 18 also had two or more significant findings on the bronchoscopy. Um, we do know that tracheomalacia does improve with time and growth. Uh, however, severe malaia often requires additional surgery, can require tracheostomy, and long-term mechanical ventilation. Um, so, while previous studies have shown a rate of tracheostomy in patients with tristomy 13 and 18, somewhere around 17%, um, this series of patients, uh, seen at Cincinnati Children's, uh, was actually 65%, uh, needing tracheostomy, and almost all of them required mechanical ventilation going forward. Um, and I think it's important to bring this up, um, because for these patients, that's an important consideration for what their quality of life is and what the family's, um, ability is, um, and willingness to take care of, uh, complicated, um, A medically complex patient at home because to take a patient home with mechanical ventilation requires significant resources and, uh, whether that's nursing support, um, potentially a parent taking off work. Um, so as some of these patients, uh, continue to have more and more, uh, intervention and care, um, I think it's important to talk about how we're counseling families, um, to include this possibility of needing a tracheostomy going forward. Well, not common, um, for patients with trisomy 13 and 18 to have hepatoblastoma. I just wanted to bring it up as a, a special consideration, uh, because, uh, just like Doctor Snowda mentioned, some impressive survival, uh, Outcomes with uh cardiac surgery in the right patient. Um, there have been significant improvements, uh, in how patients are doing following surgery and chemotherapy following, uh, hepatolastoma and other cancer diagnosis, uh, such as a Wilms tumor. And overall, a diagnosis of trisomy 13 or 18 doesn't preclude resection with a curative curative intent for these patients, but just like with cardiac surgery, uh, it's important to take the individual patient uh considerations into account to make a a multidisciplinary decision. Um, in this, uh, largest cohort of patients with trisomy 18, um, this is a pooled analysis of 70 patients, um, from across the world, um, many of whom were in Japan, um, and they identified, uh, 70 total patients. This is all patients with trisomy 18. Um, a smaller percent in this group, 15%, had, uh, mosaic trisomy 18. Uh, the median age of diagnosis was, uh, just over 11 months. Um, and in these patients, uh, 64% had surgical treatment. Um, of note, the tumors, uh, for this cohort were more solitary, less less multifocal, and were smaller tumors overall. Now, we have instituted screening for hepatoblastoma for patients with uh trisomy, um, 18, but only 1/5 of these were identified through screening. So this is still uh early identification of these tumors, um, so it's that they're smaller. Um Of note, um, the most common reasons why patients did not, um, pursue surgery, uh, were severe cardiopulmonary comorbidities, um, very severe advanced hepatoblastoma, um, and the family's decision. Uh, but there have been patients with trisomy 18 and hepatoblastoma who have undergone a liver transplant, um, in order to provide, uh, the curative, um, treatment for their hepatoblastoma. Um, overall, there was favorable, um, long-term survival with multi multimodal treatment that includes both surgery and chemotherapy. Um, in this group, uh, the survival at 5 years was 43.7%. Now, if you compare that to patients without trisomy, uh, 18, that would be 76.65-year survival. Um, but when you put it in context, um, overall, I think that is, uh, quite high. Um, next, um, we'll turn it over, uh, to Doctor Greek. Hi, everyone. Um, thanks for having me, uh, join this talk today. Uh, just, um, we'll be talking over the next few minutes about anesthesia considerations. Um, initially, when I did make the slides, I separated trisomy 13 and 18. And then after making the slides, I realized that Considerations for anesthesia are actually very similar to both. Um, and so as we move along the slides, I will be talking generally about both trisomies. Um, so even though you'll see a few different slides, um, I will be talking about them, uh, together. So if you can go to the next slide, Laura. Um, I really like this slide in terms of giving an overview of anesthetic considerations and separating it in terms of system space. So this highlights various, um, systems and what systems are affected, um, and a lot of, uh, genetic syndromes, so including trisome 13 and 18. Um, and what we look at preoperatively. So, um, airway, cardiac, uh, orthopedic, neurocognitive, vascular access, and anything else. I think this whole seminar, um, has really done a great job just highlighting the multi Disciplinary care needed for these patients. Um, and so while everybody's been, um, speaking, um, and, uh, giving their, uh, professional insight into, uh, the cardiac and general surgery and genetics, um, I really think that all ties together, so. Um, really, um, these patients come in, um, in terms of anesthesia. Most commonly, I see them for ENT dental procedures. Obviously, like Doctor Snoot is saying, many, many of them have, um, congenital heart disease. So whether that is fixed prior to some of those procedures or after, um, really kind of depends. Um, but then it's for us to determine, uh, the best care for those patients moving forward. Um, they cannot be taken care of, um, in an, at an ambulatory surgery setting, um, just because of their comorbidities. So these patients need to be taken care of, um, inpatient in our main, um, hospital where we have multidisciplinary care and subspecialty, um, emergency care available. Um, preoperatively, we're really looking at, um, so cardiac wise, um, having a recent EKG echo, um, we have a lot of these patients, if not all, come from, come for an anesthesia consult ahead of time. So that way, the day of surgery, we're not canceling the case because we're missing the recent, um, cardiology visit, echo finding. Um, neurology exam. So, uh, we wanna make sure all the boxes are checked before we, uh, bring these patients in and proceed, uh, to go under general anesthesia. Um, other things to consider because they do have, um, developmental delay, um, is what are our options for getting these patients to the operating room separating from parents. Um, so thinking about premedication options, whether it's oral Versed, nasal Presodex, um, just to calm anxiety down a little bit. Um, sometimes also for parents, um, to see, um, their, um, you know, babies or kids, um, a little bit more calm before heading back and separating from them. Um, other things, we, uh, need to look at airway assessment. A lot of times, we cannot even get an assessment. Um, so just looking at facial features and whether they've had prior anesthetics to see what, um, airway exam, um, you know, what the airway exam was before and, uh, what, um, you know, their airway look like under anesthesia at a prior, um, for a prior surgery. Um, if they do have, um, cardiac disease, um, we have cardiac anesthesiologists available. So they are subspecialized in pediatric cardiac anesthesia. So having a discussion with that team as to whether it would be helpful for them to manage the anesthesia, um, as opposed to a pediatric anesthesiologist. Um, so we do have, uh, an expert team available. Uh, moving on to intraoperative. So, many of these patients, so I'm talking about both of these groups now, um, have clefts, have retro micronathia, as, uh, Laura had already talked about, um, probably have had some ENT, um, visits in the past. But how do we intubate these patients? Um, can we even mass ventilate these patients? Um, so, previous studies have found that, um, Mask ventilation in trisomy 13 and 18 patients was found to be nearly 30-fold higher in terms of being more challenging compared to um other patients of their age and weight. Um, so considering, um, how we're putting these patients to sleep, how are we getting their airway, who is available to help in case we are having challenges with mask ventilation and intubation? And in terms of help, I'm talking a pulmonologist, ENT specialist to come in and, and be available or as a backup. Um, And what Doctor Sonoda was saying, um, these patients are, uh, you know, have cardiac issues. Um, they, they are very, um, I guess, you know, tentative in terms of their systemic pulmonary circulation. So, going to sleep with high-dose inhalation anesthetics, IV anesthetics. Which can alter blood pressure, um, pretty significantly. So really careful inductions in these patients and trying to avoid hypercaria. Um, we really don't wanna see pulmonary hypertension in the operating room, um, because, uh, once, once that happens, it's really challenging to manage. Um, so, I think, uh, as a whole, planning, planning, planning is the, is a big thing for anesthesia. So, what has been done before for these patients? Are they, um, medically optimized as they can be at that point? Um, what can we do for the airway, um, separation from parents? And then the intraoperative, intraoperative management is key. Um, extubation can be challenging. Um, so depending on their pulmonary status, um, they, some of them, if it's a bigger surgery, may need to stay intubated for a period of time. Um, and then really managing because they have, um, central and obstructive sleep apnea, um, managing, um, opioids. Um, and trying to prevent hypoxia and hypercardia in these patients, uh, postoperative, postoperatively is really important. There have been some papers on opiate, opioid-free anesthetics. Um, so use of, uh, other adjuvants, IV Tylenol, um, uh, uh, Toradol if we can. Um, so, other medications and just kind of thinking outside the box, um, in terms of trying to prevent, uh, post-op sleep apnea is very important. Um, that's a very general overview, um, but I think, um, support services, um, planning, planning, multidisciplinary care, and everybody kind of working together for these patients, um, really has, has helped, um, with their overall care, um, in the operative setting. Thanks, Laura. Thanks. Uh, in summary, um, we talked about that patients with tristomy 13 to 18 have a high rate, uh, of needing surgical intervention, um, especially when we get past that kind of initial curve of where, uh, patients aren't surviving. The most common procedures are G tubes, uh, GJ tubes, traches, ear tubes, sometimes spinal fusions, and hernia. Repairs, and overall, I think that the elective surgeries, even simple, straightforward surgeries like a G tube can be delayed following a planned cardiac repair, um, as long as that's a candidate for this. a particular patient. And that way you avoid, uh, potential anesthetic risk, um, by performing that surgery early. Um, and as Doctor Purri talked about, the anesthesia team should definitely be aware of congenital heart disease, uh, for each individual patient and the associated airway challenges. Thanks. I wanted to mention, sorry, one more thing, that regional anesthesia is an, is always uh another option too. So if, you know, you can maybe do a caudal in these patients, do a nerve block, um, that can also eliminate some of that risk of the post-op apnea with opioid use. All right. Thank you all. There is one question um from Molly in the chat, Doctor Galansky. I think she wanted to clarify. Um, did we, did you say we've seen 65% of tracing 18 and 13 patients requiring tracheostomy? Of the patients, um, that had an airway evaluation, um, so I didn't specify it, but of those patients that got the bronchoscopy, um, at our institution, so they had to have a reason that they were getting, um, an evaluation and family was interested in pursuing some further intervention enough to go through the scopes. Um, of those patients, 65% further went on to get a tracheostomy. Thank you. And then, um, a question from Mira. In low birth weight children with trisomy 18, what are your choices for GJ tubes? Yeah, our preference is for G tubes, uh, over GJ tubes, um, if possible, uh, given the risk of perforation with GJ tubes. Um, we use a weight cutoff here, um, that patients have to be, um, uh, 5 kg, um, because. Because of the risk of perforation when going straight to a GJI tube. So if patients aren't able to tolerate, uh, feeding into their stomach, uh, then we can sometimes just consider a fluoroscopic placement of a nasojujunal tube if they need post pyloric feeding in order to get them bigger. Great. Thank you both. I'm not seeing any additional questions at this time, so I think we can move on um to our next, um, speaker.