Biliary Atresia, Appendicitis, Intestinal Failure, and Anesthetic...

Stay Current is a multimedia publication designed to keep healthcare professionals up to date with standards of care and new emerging ideas. Stay Current is created and edited by Todd Ponsky, Nicholas Bruns, and Ian Glenn in partnership with Globalcast MD and is recorded and produced at Akron Children's Hospital in Akron, Ohio. Welcome to Stay Current in Pediatric Surgery. This is Nicholas Bruns, one of the founding editors of Stay Current. Today's episode is our first audio journal club. We're discussing 5 papers today with our guests, Doctor Dan von Almen, Doctor Witt Holcomb, and Dr. Aaron Lipscar. Links to the papers may be found in this episode's description. We begin now with Doctor von Almen. Welcome to Stay Current, and in this episode we're going to be doing our first audio journal club, and the purpose of this audio journal club is to review key articles in a very brief amount of time to address what are key things that we should be knowing as pediatric surgeons. We may not have time to read all of the literature, so hopefully by doing these journal clubs, we should be able to uh. Explain all of the different uh key things that have been developed in the last year or two, and um the first topic that we're going to be discussing is, is the use of corticosteroids and biliary atresia and presenting this paper, we have Dr. Dan von Almen, and Dr. von Alman is the director of the division of Pediatric General and thoracic Surgery and professor at University of Cincinnati Department of Surgery. Dan, thanks for doing this today. My pleasure. So what did you find in this article? So the paper, the title of the paper is The Use of corticosteroid steroids after porterenterostomy for bile drainage in infants with biliary atresia, or the START Randomized Trial. The lead author on the paper is Georgie Bezarra from Cincinnati, and the senior author is Ron Sokel from Colorado. This paper is the product of a multi-institutional group called the Childhood Liver Disease Research and Education Network, and this trial was a randomized trial to look at the use of steroids in biliary atresia. The hypothesis of the trial is that steroids given after Porter entererostomy impact the outcome, both with regard to bile drainage as well as liver survival. The objective was to determine whether high dose steroids are better than surgery alone for biliary atresia and survival of the liver after Kasai. The methods that they used involved this multi-center randomized double-blind trial in which 140 infants were enrolled. There were 257 patients identified, and 140 were randomized with 70 in each group. There was excellent matching of the groups with regard to their clinical status at the time of enrollment. The intervention involved participants were randomized to receive intravenous steroids for 2 weeks, followed by oral steroids for 2 weeks, followed by a taper over 9 weeks, so a total of 13 weeks of steroids that were initiated within 72 hours of the hepato porter enterostomy. The outcomes of the study were several. The primary outcome was to look at the percentage of participants with a serum total bilirubin level of less than 1.5 mg per deciliter with his or her native liver at 6 months post hepato porter enterostomy. The study was powered to detect a 25% absolute treatment difference. The secondary outcomes were also important, and these involved survival of the native native liver at 24 months of age and the incidence of serious adverse events. The results of the study showed that the high dose steroid therapy following surgery did not result in a statistically significant treatment difference in bile drainage at 6 months, with the treatment group having an incidence of 58.6% versus 48.6% in the placebo group. It was also true when the patients were segmented into those who were younger than 70 days at the time of Kasai and those who were over 70 days at the time of Kasai. So in both of those age groups, treatment versus placebo did not make a difference in outcome. Although a small clinical benefit could not be excluded. The outcome of survival without liver transplant at 24 months of age was also not statistically significantly different between the two treatment groups. The rate was 58.7% for the steroid group and 49.4% for the placebo group. As far as adverse events go, they were common in both groups, with a near 80% incidence in both patient populations, which they attributed to be largely reflective of the fact that they had severe underlying liver dysfunction at the time of surgery. Steroid treatment was associated with an earlier onset of serious adverse events in children with biliary atresia, although the overall adverse event numbers were not statistically different. This is a fascinating paper. What are your general thoughts about it? So I think it's a, it's a really important paper and this is a really significant issue that I think everybody who does a Kasai wrestles with this question of whether steroids should be used or not, and I personally used to use them in my practice, but based on this study have stopped using them, and I think That it gives, it is a very well constructed, very well run study with, with very sophisticated statistics and a good randomization scheme that I think provides the best data in the literature to suggest that there is not a statistically significant difference when steroids are given versus when they are not. So Dan, teach me here because I'm reading this paper and I'm not as convinced as you, uh, so I want to better understand because all the smart people I know who read this paper have stopped using steroids. I'm the only one left still using them. So, uh, what I'm reading here is that there were a higher percentage of patients that. Uh, achieved drainage in the steroid group. Now, I get that that's not statistically significant because they did power the study for a 25% difference, and this was only 10%. But given that the complications were about the same, I mean, the steroid group did have a high earlier onset of, of cholangitis, but the total number was the same. Why not give the steroids? Is it, is it that you, it's an unnecessary treatment and so we shouldn't give it? Or do you, are you afraid of something? Or why, why, why not give them? So I think it really comes down to whether you think that the 25% difference is the right, uh, is the right metric to use for whether steroids. are worthwhile or not and whether that is a clinically significant difference. And the authors of the paper, and I believe them, feel that anything less than a 25% difference is probably not worth the potential risk of the early complications associated with the steroids. And so because the the results did not Prove that a greater than 25% difference was present, then the author's argument is that it's not worth the potential early complications associated with the steroids. More importantly, if you look at the overall liver survival, which is the ultimate outcome, You know, to avoid liver transplant, that is clearly not different between the two groups, right? Right. So using that as the outcome, there's no difference. And so why add a whole other therapy, right? I mean, the whole point of this is to preserve the native liver. I mean, you could also make the argument that in the data there was about a 10% difference if you looked at The bile bilirubin level in the patients who were treated with steroids was about 10% lower than the patients who were not treated with steroids up for their duration of effect of maintaining a low bilirubin level. However, again, at the outset, I mean at the termination of the study, the transplant rate was the same. So the use of steroids, is it um proposed that, and, and you may not know this answer, but uh because a lot of this is theoretical, is it proposed that the process of the atresia is still ongoing and the steroids may prevent further development of the biliary atresia process, or is it to protect the anastomosis? I think there are two mechanisms that are proposed as the physiology through which steroids might impact the outcome in this disease process. One is, is that, as you alluded to, this is an inflammatory process, and it's still ongoing, and that the steroids reduce the inflammation and preserve some of those little ductules to which you do your portoanerostomy. The second effect is that steroids are a known chouretic, and so essentially it's giving a, it would be like giving a diuresis after a kidney transplant to maintain urine flow and that you're maintaining bile flow by giving the steroids and that that would ultimately help that flow to be preserved. That's great. That was a great summary of it, and it certainly helps me understand, and I think just to summarize here, what I'm hearing you say is that uh surgeons listening to this should know that the literature is pretty clear here that there is no added benefit that has been demonstrated of steroids in patients with biliary atresia after Kasai. Is that correct? I think that's true. I think that you have to always be careful about generalizing studies, and in this study it is specifically testing a fairly long course, 1413 week course of high dose steroids, but in that patient population with that treatment regimen, there was no difference in the long term outcome of the need for liver transplant or death. Well Dan, as always I appreciate you, uh, always contributing to these new methods of education and I appreciate you taking the time to uh. To present this article to everyone and hopefully we'll do more of these again in the future. My pleasure and I look forward to it. This concludes Dr. von Almen's discussion. We now continue to Dr. Holcomb's discussion. And with us today we have Dr. Witt Holcomb, who is the first podcast faculty that we've had, uh, who originally did appendicitis, and uh today, Dr. Holcomb, who is the surgeon in chief at Children's Mercy Hospital in Kansas City, uh, is going to be reviewing two articles for us. So, Witt, thanks for joining us today. Thank you, Todd. I'm glad to be here. So what you got today? What articles are we looking at? So there are two articles. The first article is entitled Comparative Effectiveness of Skin Antiseptic Agents in Reducing Surgical Site Infections, a report from the Washington State Surgical Care and Outcomes Assessment Program by a number of physicians led by Dr. Hakarainen. This article was published in the Journal of the American College of Surgeons, March 2014. The article is an interesting paper, um, in that it comes from a prospectively gathered clinical clinical registry. That includes more than 50 hospitals in the state of Washington. The authors performed a cohort analysis to evaluate the relationship of four commonly used skin antiseptic agents and looked at their effectiveness with surgical site infections. And that'll be abbreviated SSI going forward. Now these are mostly adult patients, and they're going undergoing clean contaminated operations over an 18 month period beginning January 2011. The authors also wanted to look and see whether isopropyl alcohol had a unique and beneficial effect on SSI. Again, it's important to emphasize, emphasize for our audience that these are general surgery procedures in adults. 60% of the cases were colorectal in nature, 34% were bariatric, and 6% were deemed to be other. All the cases were classified as clean contaminated. In this registry data, the overall rate of SSI was 4.6%, but this differed between colorectal, where it was 6.6%, bariatric, where it was 1.4%, and 1.5% in the other cases. The primary outcome variable in this study was SSI during the index hospitalization. Now what did the authors found? They found that they could not identify a single antiseptic agent that was associated with a lower risk of SSI than any other agent. They also found that the unadjusted rate of SSI in the agents that did not have isopropyl alcohol was 4.5%, and that was compared to 4.6% with the agents who did have isopropyl alcohol as part of the mixture. Thus they found no benefit in having isopropyl alcohol as as part of the antiseptic agent. Now a few comments about the paper. One of the limitations of the paper was that the registry data could not identify an SSI if it was diagnosed after discharge. And therefore these data probably underestimate the true rate of SSI in this risk classification scheme. As another recent report showed 50% or more SSIs are diagnosed after discharge. The commonly accepted time frame from which most SSI occur is 3 to 3 to 10 days after operation, and in this particular study, the average length of stay among the patients was 6 to 7 days. Another problem with this study is that there was a wide variation in the use of antiseptic agents across hospital sites, as well as the type of general surgical procedure performed, and there was also significant variability in the populations that were being used for each anesthetic, antiseptic agent group. So in conclusion, this is a prospectively gathered data registry looking at SSI for clean contaminated cases. There were no benefits to one antiseptic agent over another, and isopropyl alcohol did not offer any added benefit either. Again, this study is an adult and dealt primarily with colorectal and bariatric cases. So that was a great summary and um I guess my question for you is, uh, you know, one of the things they compared was as you said, it sort of the uh iodine type solution versus a chloroprep um type of solution and I know at at our hospital they've made us switch from the iodine base to the chloroprep because they said that studies have shown decreased um site infections, so. I guess my question is twofold. What do you do in your hospital, and will this article change your practice? In our hospital, we also have changed to chlorhexidine and isopropyl alcohol, and we've continued to do that except in cases where we want to prep out a mucous membrane. A, a part of the body. So for instance, a circumcision, we wouldn't necessarily do that in or or some other area that we wouldn't want to necessarily get the chlorhexidine in it. Now it's important to realize that most of the cases that we perform in pediatric surgery are clean cases and so this article really does not. Uh, uh, address clean cases, but it addresses clean contaminated cases. And so we continue to use the, uh, the chlorhexidine or chloroprep just as you are and have found that we've not noticed either an increase or even a decrease in SSI, at least in our institution, with that change. And so, um, with, with, uh. This article, I know this is clean contaminated. At least I can say that, you know, um, if they want to use the iodine type solution, at least for a clean contaminated case, it's probably not a huge problem. And man, those 3 minutes are sometimes pretty hard to wait for. So, uh, it's always, it would be nice to use the beta, the betadine type solution, um, but I guess for now I'm going to stick with the. The, the chlo chlo chlorprep or whichever is the chlorhexidine with isopropyl alcohol. Right, that's, that's correct. I think that a lot of things are now being known about preps, and as you mentioned, uh, one aspect of using the, uh, betadine or iodine preps is that it needs to wait and dry, and usually it takes 3 minutes or so. So the case can get started a lot faster if you use the chloraPrep or a similar agent. And if you're doing 6 or 7 cases a day, every minute seems to help get the cases moving along. So there is an added benefit that the chlorprep or similar agent does dry faster than the betadine or iodine prep solutions. Let me clarify this because I want this is actually an interesting point. So for us, and I think you said something that I probably do wrong, for us it's the opposite, that the chloraPrep. Uh, we have to wait 3 minutes for it to dry, and the Betadine, I don't. I just go, just paint it and go. Um, is it, and I've heard from people saying that you're supposed to wait for the Betadine to dry as well. Do you, do you, uh, is your chloro chlorhexidine type solution, uh, one that you don't have to wait 3 minutes, or do you wait for both about 3 minutes? Well, in, in practical terms, the, the chloroprep or a similar agent dries faster than the betadine does. And so we generally want to make sure that the betadine prep is dry. And so we, we generally wait. Uh, several minutes to make sure that's dry as opposed to the, uh, chloroprep or similar agent, uh, dries faster and it seems like we're able to go on and get started, um, uh, faster than we would with the Betadine, OK. Well, that was a good discussion and I think this will probably be revisited every few years uh going forward as it always is. Um Let's move on to the next article. What was the, the next article that you were going to review? So the next article is entitled Non-operative Treatment with antibiotics versus surgery for acute non perforated appendicitis in children, a pilot randomized controlled trial. This paper, uh, is, uh, a multi-institutional. Uh, group of authors, uh, from, um, Stockholm, uh, Great Ormond Street, uh, Toronto. And, uh, was published in the Annals of Surgery in 2015. Uh, so, uh, this is a, uh, a good study to discuss because it's a harbinger of things to come. Uh, the authors report a pilot study, and it's a pilot study because there was no power analysis performed. The patients in this study were between 5 and 15 years of age, and they had non perforated appendicitis based on imaging studies. So it's important to remember or realize that we're talking about non perforated appendicitis. Uh, these were patients who otherwise would have undergone a laparoscopic appendectomy. And they were randomized to either non-operative management with antibiotics or to laparoscopic appendectomy. The follow-up time period was one year. It's important that the authors develop discharge criteria for both arms of the study. And that included the patient being afebrile for 24 hours, the patient having adequate pain relief on oral analgesics, the patient tolerating a light diet, and the patient being ambulatory. Their primary outcome variable was the number of children in each group who achieved, as they called it, resolution of symptoms without significant complications. Secondary outcomes included median time to discharge as well as cost. Now, during the time frame of the study, uh, and it's a recent study as it, uh, was just published earlier this year, there were 225 children seen with a diagnosis of appendicitis, and exclusion criteria eliminated 57 patients. In addition, 77 patients and families declined to participate. 37 patients were not, were not asked. Two were excluded by the investigator, and then there was one randomization failure. So they randomized and their plan was to perform the study on 50 total patients. 26 were randomized to operation and 24 were randomized to non-operative treatment with antibiotics. Two of the 24 patients in the non-operative treatment arm underwent laparoscopic appendectomy within the time frame of the primary antibiotic therapy treatment course, and one patient underwent appendectomy 9 months later for a recurrent acute appendicitis. However, it's important to realize that another 6 patients had an appendectomy due to recurrent abdominal pain or parental desire during the 1 year follow-up time period. None of these 6 patients had evidence of appendicitis on histologic examination. So I disagree a little bit with the author, one of the author's initial conclusions, and that was that 22 out of 24 patients, that is 92%, treated non-operatively, and had initial resolution of symptoms with only one patient having a recurrence during the follow-up period. So in my looking at it, a total of 9 of the 24 patients initially randomized to. Antibiotic therapy underwent appendectomy at some point in the first year of the study, so that the failure rate, at least from my perspective, is really 38% and the success rate of non-operative treatment is 62%. Other findings included the fact that the median time to discharge was significantly shorter in the surgical group than in the non-operative treatment group. However, this may be because there was a stipulated 48 hour minimum hospitalization for those in the non-operative management group. Also, the cost for the initial inpatient stay was interestingly, significantly lower in the non-operative treatment group than in the group undergoing operation. This is in spite of the fact that their hospitalizations were longer, and it points to the fact that undergoing an operation can be costly when compared with non-operative management. So in conclusion, this is a good pilot study, and it shows that a definitive randomized trial comparing nonoperative treatment with antibiotics and laparoscopic appendectomy for non-perforated appendicitis would be safe and feasible. And in fact such a study is already planned between these authors and several other centers, and in fact our center will be participating in this trial. Mm, so I, I'm very excited about this paper. I think this is one of these topics that's been pretty hot lately and will continue to make a big impact in our profession. Obviously this is just a pilot study and they. They really need to look at a very long term follow up to, to look at if you're truly going to compare operative versus non-operative, they need to look at the incidence of bowel obstruction after surgery to see what the complications would be from that operation. Likely they might get bowel obstructions after non-operative management as well by leaving in the scarred appendix. You know, what, I'm wondering at your institution, I know you're going to be part of the upcoming study. Have you ever treated patients non-operatively with acute appendicitis? No, we have, uh, we have not. Yeah, I haven't, but I know people who have been treated non-operatively because they were a poor operative candidate and they did great. Um, so at least it's helpful to know that in a, in a situation where someone may not be the best operative candidate, even though the data is not pure yet, there's evidence to suggest that in the majority of patients it may be safe. Would you agree with that? I would, yes, I would agree. The patient population that comes to mind that we do treat sometimes non-operatively is the immunosuppressed cancer patient who has tiphitis. Now tiphitis is not appendicitis, but it's somewhat close, and most of the time those patients, their inflammation resolves with antibiotics. Uh, so, I have not treated someone non-operatively, but the literature is beginning to tell us that a certain population of patients can probably be treated. The trick for us will be to figure out which population can be treated successfully and which population should undergo the undergo the operation relatively soon after presentation. Yeah, I agree. And the other thing is the most important part of any trial will not, will be the follow up period, and it's, it's hard to know even if you have, say, a 5 year follow up period or even 10 year follow up period. Most patients in such a trial will only be 15 to 20 years of age with a 10 year follow up, and so they're going to live for another 40 or 50 years. And so. Are they at risk for developing appendicitis, you know, after they get out of the pediatric surgeon's age group, and so it'd be really important to try to follow these patients for a very long time, and we may not even see the answer in our lifetimes, but it may be apparent in our The next generation's lifetime. No, I think that's right, and we were just sort of saying they're going to have to republish every 10 years to show what the real numbers are, you know, one of the things that was disconcerting was that that you highlighted was the number of patients that Didn't have active appendicitis but required the appendix to be removed because of abdominal pain. It's almost like non-operative neck, you know, you can get through the inflammatory phase, but they probably have some scarring and stricture of the appendix, which can lead to subacute pain and ultimately to recurrent appendicitis when they're older. So that, that is a very real thing that may present 40 years later, like you said. Yes, and a, and a few parents in this study, remember, only 24 patients were randomized to non-operative management, but a few parents really wanted their, their child's appendix out so they wouldn't have to worry about it. And if you think about it, if we can take the appendix, if we can see the patient, assess them, take the appendix out within a few hours, and then discharge them that same day. It's sort of like an outpatient procedure and it may be difficult to argue against just doing that versus treating them for a day or two with antibiotics and then wondering whether they're going to relapse the next week or next year or 10 years later. So I really believe that an important aspect of any study will be getting the parents' perspective on treatment, whether it's operative or non-operative. Yeah, no, I think that's a great point, Witt. As always, we really appreciate you always taking the time for these academic endeavors, and everyone loves to hear your thoughts on things. So we appreciate the time to review these articles and present them for us. So I hope you have a good rest of your day. Thanks very much. I've enjoyed doing this. Thanks, thanks so much. We'll talk to you soon. OK, bye bye. Bye bye. This concludes Doctor Holcomb's discussion. We now continue to Doctor Lipsgar's discussion. Today we have with us Dr. Aaron Lipscar, and Aaron's going to go over two articles that are very relevant to pediatric surgery. Aaron, welcome and thanks for joining us today. Thank you, Todd. Erin, can you first tell us a little bit about yourself? Sure, my name's Aaron Lipskar. I'm an assistant professor of surgery and pediatrics at Cohen Children's Medical Center in Long Island, part of the North Shore Long Island Jewish Health System. Perfect. Tell us what article you're going to be starting with today. First we're going to be looking at an article from the Journal of Pediatrics from July of 2015 titled The Predictors of Enteral Autonomy in Children with Intestinal failure, a multi-center cohort Study. This is a study put together by the Pediatric Intestinal Failure Consortium, or PIFCON. A which consists of 14 multidisciplinary intestinal rehab programs around the country. 9 of these 14 sites also had affiliated intestinal transplantation programs. Just to be clear on some definitions throughout the paper. Intestinal failure was defined as severe congenital or acquired gastrointestinal diseases during infancy with dependence on parenteral nutrition for more than 60 days in a 74 day period, and enteral autonomy was defined as a parenteral nutrition discontinuation for a time period of greater than 3 months. OK, so what'd they find? What did, what did the studies show? So this really what they tried to do is describe the cumulative incident of achieving enteral autonomy and identifying patient and institutional characteristics associated with enteral autonomy from this very large cohort of children, and they did a multi-center retrospective cohort analysis from their consortium. They were able to accumulate 272 patients for a median follow-up of 33 months, about 3 year follow up. They found that enteral autonomy was achieved in 43% of their cohort, which fits with much of the data that's out there. 13% of their patients remained parenteral nutrition dependent, and 43% of patients either died or underwent transplantation. What they, what they found was that Patients with an underlying diagnosis of necrotizing enterocolitis or care at an intestinal rehab facility without an associated transplant center and patients with ileocecal valves all attained enteral autonomy at a statistically significant higher level. And when they looked at a separate set of data of the of those kids who had residual small bowel length measured, that additionally was a statistically significant variable to attain enteral autonomy, although not, not quite as impressive as the other three variables. What's interesting about this paper is that multiple reports have demonstrated the importance of residual bowel length on outcome. And but the data on the impact of the ileocecal valve on adaptation has been more variable, and here they really found a benefit of having an ileocecal valve. To me, one of the interesting parts is this protective effect of necrotizing enterocolitis, which in some ways goes against some of our understanding of that inflammatory illness, and it really shows us how much we have to learn. About intestinal failure and what the risks and probabilities of enteral autonomy are. It's really cool because I have to tell you they basically as you just said, really that goes against the two things that I would have guessed that necrotizing enterocolitis would have had a poorer prognosis and that I thought that we had been more and more thinking that the ileocecal valve did not have as much of an impact as we thought, but it looks like this paper disproved both of those things. Yeah, this paper sort of gives us a lot of information that that we need to start doing a prospective look between this consortium, which is what their, which is what their goal is to really have a better understanding of it, and then, and then, you know, just to really teach us how much we have to learn in this same journal from the same institution with the leading institution of the of the PIFCon Group was a paper looking at how necrotizing enterocolitis was a poor predictor of growth outcome in infants with short bowel syndrome. So the two things are are presented right back to back in the same journal, which is a really interesting concept. Wow, that's great. And which journal was this from again? This is the Journal of Pediatrics, July of 2015. OK, great. So tell me, I mean, how is this paper going to affect your management of patients? In many ways it it it doesn't. There's a very interesting part of this that I think intestinal rehab programs think about a lot, which was this what appeared to be a protective effect of being in an intestinal rehab program that does not have an associated intestinal transplant program. There's been criticisms that perhaps the existence of the transplant program biases an institution towards transplant, but when you look at the patients, the residual small bowel length, the presence of an ill leak bowel, they seem to get sicker patients at the intestinal, at the transplant programs. So it's hard to make sense of that data. I think what this paper really changes is the importance of children with intestinal failure and what we call short gut syndrome to really have the opportunity to be managed in one of these multidisciplinary intestinal rehab programs, because the combination of eliminating collapses and and cholestasis prevention is really going to has changed how we understand enteral autonomy and intestinal failure. That's a great point, and that was a great review. Tell me what you got for the second article today. The second article is a bit of a controversial article. It's actually a perspective article from the New England Journal of Medicine in February of 2015 titled Anesthetic Neurotoxicity Clinical Implications of Animal Models, and its authors are from both the FDA and Northwestern University, as well as WashU. And University of Toronto and it really touches on an important topic for our, for us as pediatric surgeons, which is the potential toxicity of general anesthesia on the developing brain. So to give some background on the paper, in 2009, the FDA established a public-private partnership with the International Anesthesia Research Society called SMARTTTs, or Strategies for Mitigating Anesthesia-related Neurotoxicity. And Smart Tots in 2012, along with the AAP released a consensus statement that summarized the state of knowledge and presented some recommendations. And although there was insufficient data at that time to draw any firm conclusions, the consensus statement recommended that perhaps the elective surgical procedures that were performed under anesthesia be avoided in children less than 3 years, and it really called for further research. And since then, a significant amount of animal as well as observational population-based studies have been undertaken. Some of the new animal studies have confirmed that the commonly used anesthetics and sedatives that either increase inhibitory GABA receptor activity or block excitatory glutamate receptors. This includes, by the way, propofol, atomidate, sevoflu. Fluorraine, isoflurane, and ketamine produce profound neurotoxic effects in laboratory animals ranging from nematodes to nonhuman primates. There are problems with many of these studies. Some of these medications are given at high doses for long periods of time, but the evidence is quite compelling. And this compelling evidence is supported by a small number of observational studies in children who undergo anesthesia early in life, and these observational studies offer conflicting results, and they're confounded by multiple factors, but they do suggest that some children may have deficits, although it's very difficult to show a causation, if anything, just an association. Nevertheless, in June of 2014, Smart Tots convened a meeting to review the data. That has accumulated and they released a new statement. They concluded that the current data from animal studies is now sufficiently convincing that large scale clinical studies are warranted, and they produced a new statement recommending that surgical procedures performed under anesthesia be avoided in children under 3 years of age unless the situation. I urgent or potentially harmful if not attended to. The statement also emphasizes the need to determine whether anesthetic and sedative drugs cause brain damage in infants, toddlers, and children. You know, Todd, this is a big problem for us because it really would change how we practice pediatric surgery, and there are very important fundamental questions that remain to be answered. We hope that a combination of animal studies and well designed clinical trials will help, and there does seem to be mounting evidence that there is some neurotoxic effect of general anesthesia on the developing brain. So the authors conclude that in the meantime, while we're accumulating this data, parents and care providers should be made aware of the potential risks of these anesthetics. And that that surgeons, anesthesiologists, and parents should carefully consider how urgently surgery is needed, particularly in children under the age of 3. Erin, I think this is of the articles that we reviewed recently, probably the most talked about topic in the last 6. Months to a year, you know, obviously we don't know really any hard facts yet. We don't know anything for sure, but I certainly am noticing a trend towards delaying elective surgery. Let me ask you, in general, do you ever delay an inguinal hernia repair for anesthetic concerns? I have yet to delay an inguinal hernia for anesthetic concerns. I think that it's something that we are going to have to look at carefully as pediatric surgeons. I think a more difficult question would be a circumcision under general anesthesia. That's a great question. How do you do your circumcisions there at North Shore? unless outside of the neonatal period they're done with a general as well as regional anesthesia, and that leads me to the concept of regional anesthesia because that that's really a field that I'm hoping it changes how we deliver general anesthesia to our patients. I find a lot of the correlations within this debate to the what happened with the CAT scan radiation risk debate, and I'm hesitant. To make too many changes without solid data as we completely changed how we work up appendicitis based on unclear data of cancer risks from radiation, but nevertheless, Things like Presodex and regional anesthesia will help us decrease the amount of general anesthesia we can give in many operations. In almost, almost every laparoscopy laparoscopic or thoracoscopic or open operation, there is a regional block that can diminish the amount of potentially neurotoxic medications that need to be administered. Yeah, and I think that's a great point. At our hospital, our chief of anesthesia anesthesiology said that you give us the rule of two that try to defer elective operations till after 2. I know the article said 3, but that's our rule, and try not to have two anesthetics in a year. So dermoid cysts now. I just saw one last week. She was 6 months. I told them come back in 2 years, you know, in 1 year and a half years. I think that with hernias we know there's a risk of waiting. We don't know the risk of the anesthesia yet, so I don't even let that come into play because the younger they are, the higher risk of incarceration, you know, then also the higher risk of an anesthetic complication, but I don't have that impact me at all, you know, there's another piece of this that is very important. I actually have a uh A paper being presented at AAP within the manuscripts in progress of what parental perceptions of the risks of anesthesia are because it's an interesting topic that we really haven't been tried in the court of public opinion yet. There have been some articles in press, but Hasn't reached prime time and and and it will, and I think we need to be prepared. What we found is that really as of right now it's not too much on parents' radars. We did a survey study of parents in a primary care pediatrics office. We surveyed about 150 parents and caregivers and found that the vast majority did not know that this was a major issue. Yeah, it's definitely a hot topic. I think it'll be more information coming to the parents and to us as this gets studied more. So, Erin, thank you so much for spending the time today to go over these two pretty, pretty important articles, and I hope you have a good rest of your day. Thanks, Todd. We hope you enjoyed this episode of Stay Current in Pediatric Surgery. You can listen, watch, or read all content by downloading the Stay Current and Surgery app. Please send questions or comments to us at staycurrent podcast@gmail.com. We'll see you next time.