Postoperative Pediatric Pain Practice Post the Codeine Era: Peri-Operative...

And he's going to speak to us about the post-operative pediatric pain, uh, practice. Uh, it's actually called post the codeine era. So, uh, Fareed, I'm gonna, uh, turn things over to you. Thank you. Well, thank you very much, Doctor Ponsky and Doctor Duncan, for, uh, inviting me. Uh, this is an honor for me to speak to, uh, to this group of audience here. Um, Obviously I, I think I'm lucky to be the closer here because many of the things I wanted to say already very well covered, uh, by the experts here in, uh, in the studio and the experts, uh, with us in the faculty by Doctor Joshi, Doctor Simpson, Doctor Burton, and Doctor Feldman as well. I will try to focus more on the pediatric section of my presentation. So I might go fly quickly through certain slides and might spend a little bit more time on others. Um, so some basic principles historically, obviously, the children's pain has been always undertreated. Um, assessment and management of a child pain is very different from that of an adult because of cognitive, behavioral, emotional differences, as well as anatomic and physiological differences. What is the scope of undertreatment? In 1968, uh, Swafford and Allen, they wrote only 2 out of 60, only 2. So that's 3%, uh, children will require pain medication following general surgery, stating that pediatric patients seldom need medication for relief of pain. They tolerate discomfort very well. Uh, I would say it was until the 1990s when the real revolution on pediatric pain management started. What are the explanations for undertreatment? Some incorrect assumptions like there is a correct amount of pain for an injury, and children's nervous systems are immature. They have no memory for pain. They metabolize opioids differently. They might get addicted sooner. Pain is difficult to assess in children because they cannot tell us, and we don't understand their language and the extent of their discomfort. And always there was a challenge that there is no single universally acceptable pain assessment measure for kids. The optimal relief of pain in pediatric care starts with the recognition that an individual child is being assessed and treated, not pain as a symptom apart from the child, 1998 by McGrath. What are the cognitive factors? Understanding about the pain source, ability to control what will happen, expectations regarding the quality and strength of pain, previous experience, that previous experience point here, I, I really put a lot of stress on it because we do. See kids, uh, multiple occasions like, I, I many times I go to the room and I say, uh, how many times have you been here? This is my 3rd or 4th, uh, visit to the hospital. So it's very important to know if there was a successful, uh, previous experience with pain management that we can duplicate knowledge of pain, uh, control strategies. The behavioral factors would be the distress response. Obviously, remember, any child you are taking care of, you're basically taking care of two patients, the child, him or herself, and the family members, and that may initiate, maintain, or exacerbate any child pain. Emotional factors will vary widely, including some mutual acceptance, some anxiety, as Dr. Duncan was mentioning a while ago, and fear and anger and sadness. Um, this is probably one of the most important slides I would like to, uh, spend a couple of minutes in, uh, and, and for people who do pediatrics, this is really important because We always say children or kids are not small adults. Uh, Children have their own physiology. They have their own anatomy. They have their own things, and I would say this is very applicable to the age maybe of 8 years old. Some people will say up to 12, but I would say up to 8 or 9, those physiological changes are applicable, especially in the very first year of life. So any new need. Or infant, you have to pay so much attention to those 5 points that I will be discussing here. So for the CNS, for example, the blood-brain barrier is immature, uh, and relative maturity, uh, we reach that level at the age of about 9 months. At the age of about 2 years, you can say, OK, well this blood-brain barrier will really be a barrier to a hydrophilic drug versus a, a lipophilic drug. So for example, a fentanyl, which is a very highly um lipophilic drug, will cross the blood-brain barrier no matter what. So an adult and a and a pediatric patient will have the same amount of fentanyl crossing their brain because it's a very fat soluble drug and it will cross versus morphine. Morphine, uh when we titrate the dose of morphine, when we say it's 0.1 mg per kilogram. This dose is based on the blood-brain barrier. Preventing some part of the morphine dose of reaching the brain and causing the effect. That's why when I read Doctor Simpson's, uh, um, uh, slides, there is a slide that says 100 mc of fentanyl is equivalent to 10 mg of morphine. That's absolutely pharmaceutically correct, because we know that fentanyl is 100 times more potent than morphine. So multiply 100 by 100, it will give you 10 mg. Um, But that is not applicable in the very early few months of life, especially the first year, because that amount of morphine will not cross when the blood brain barrier is mature. But since these kids don't have a mature one, then there is a major difference, so we have to pay attention to that. When we go to the liver, same thing. The liver of those neonates is very immature, will not be able to take care of the pharmacokinetics, as we said, of a drug. Will not be able to metabolize or degrade. And as we know, there are two phases of metabolism in the liver, phase 1 and phase 2. So we have to be careful when we think about that. Also, many of the kids with abdominal issues will have relative hepatic blood flow, blood supply difference than than kids without. Protein binding is no different. We don't have mature liver, so we don't have enough albumin or alpha 1 acid glycoprotein, which will be carrying most of our medications. If you think about it, pain management. Uh, all the medications that we have been talking about, whether opioids or non-opioids, are usually bound to albumin. Most of our local anesthetics are usually bound to the alpha-1 acid glycoprotein, and it is the unbound portion of these medications that is responsible for the pharmacodynamics. Um, so, when you have a child with less albumin or less alpha 1 acid glycoprotein. You know that you will have more free portion of the drug to cause the effect. Kidney is no different. Again, the kidney is not mature until the age of about one year. Kidney cannot accept protein load, cannot. Concentrate urine cannot handle a sodium load, so we have to be careful about renally metabolized or execreted drugs. Volume of distribution is very important as well. I always remember a key sentence that was mentioned to me during my pediatric anesthesia fellowship. That we are all born bags of water and we die bags of fat. So, so what that means, what that means is the volume of distribution for a hydrophilic versus lipophillic drug is extremely important for us to understand. So you cannot apply the same rule that you have an adult for a NICU baby, for example, or an infant or any, any, any, any child about 1 or 2 years old or less. Again, some scores, FLG scale for ages 1 to 3, faces, you guys are all familiar with that stuff, visual analog or numeric scale, evaluation of pain, um, appraisal of the nociceptive stimuli, and thorough assessment of factors that modify how the stimuli is processed by the individual child. Etiology, location of pain, qualitative features, emotional status, opinions of the child and family regarding pain management and analgesic interventions. So make sure you engage the family and the child if the child, the child can participate, make sure you engage them in their own perioperative pain management or pain experience. I, can I interrupt for a second because I, I don't want to forget this point. In children it's been hard to study pain because you, I don't think you could, the, the faces or flax scale are as accurate as, um, some of the adult, um, scales, and I'm curious if you disagree with that. So I've met this guy. His name's Jeffrey Runge. He's a veterinarian. He's actually a member of SAGES and he's a member of IPEG. And he's this cutting edge guy and they, there is a great way to study pain in animals, um, and apply it to humans. And that is something called an accelerometer. And what they do is they attach a thing to the collar of the animal. And it's absolutely been validated that based on how much the animal moves after the, the drug or the procedure, they can evaluate. So a lot of movement is less pain, and they know because they do a shame, you know, they cause pain with nothing and they don't move at all. And then, so there is a developing something that we as surgeons are. We as anesthesiologists should be really using in our studies is not only just human trials but using the animals to help figure out some of our, our pain assessment. Just, I just wanted to bring that up because it was fascinating. That's a great point. I, I never heard of it, but very willing to, uh, yeah, and I'll, I'll put up those, uh, those to try, yeah. So, so we have to evaluate the pain again, as I mentioned, and, uh, uh, uh, one more time, the prior analgesic history, uh, nature and efficacy is very important. Uh, no susceptive pain. We talked about it and we, we did, uh, talk about the definition of pain. Um, Again, no susceptive pain can be somatic, can be visceral, uh, somatic, uh, bones, joints, muscles, usually aching or throbbing, usually through alpha, A delta, I'm sorry, Adelta nerve fibers, which is myelinated and fast. Visceral pain arises from visceral organs, usually intermittent, crampy, and poorly localized, usually transmitted through the C fibers, which are unmyelinated and slow. Um, we have to recognize, prevent, and, again, back to the same point, which is the multimodal therapy. I think this is the best keyword. Which is the theme of our discussion today. Treatment modalities against most of this is a repeat non-steroidal inhibition at the periphery, blocking of pain receptors through tramadol or opioids, neural blockade of transmission which is regional or neuraxial, prevention of central sensitization like preemptive analgesia or using centrally acting drugs, and prevention and treatment of an anxiety accompanying acute pain like what Dr. Burton had focused on. Preemptive analgesia, I just want to mention one quick word here. We, we did talk about the fact that preemptive analgesia is equivocal, and we don't have quite a proof for it, especially lately, but I would also say there are other frequent studies that prove that preemptive analgesia is quite effective, and many people still recommend preemptive analgesia. When I say preemptive analgesia, I also want to emphasize the fact that regional blocks, whether at the site of the surgeon infiltration or peripheral nerves or regional or neuroaxial, not just, not only have the preemptive analgesia effect from reduction of pain signals reaching the central nervous system. But also reducing the stress response. And if you think about the stress response as aldosterone, epinephrine, norepinephrine, glucagon, neuropeptide D, and all those kinds of things, these can turn to be pain modulators later. And if you can control them ahead of the game, that would be a very good idea. The World Health Organization pain ladder calls for mild pain. Use acetaminophen or non-steroidals, moderate pain with or without opioids and tramadol. Severe pain, which I agree with Dr. Simpson there, opioids always have a role in severe pain management. Acetaminophen, non-steroidals, I think we talked about them. The difference between them, non-steroidals have more anti-inflammatory action. Acetaminophen usually works centrally. Non-steroidals work peripherally. And the, the one key word that I will focus here to answer the question of Toradol, when we, I'm trying to move the air is not moving. This ceiling effect, the third point in non-steroidal ceiling effect. Dr. Joshi mentioned it. Uh, which means ceiling effect means the more drug you give, you will not get more effects, but you will get more side effects. And one of the best examples for non-steroidal ceiling effect is Toradol, and it has been studied, and this is in the pediatric literature. I, I'm not quite sure about the adult literature in that part. The dose of Toradol is no more 0.5 mg or or 1 mg per kilogram. It's 0.2 to 0.3 mg per kilogram to a maximum of 15 mg, and we usually do not give it more frequently than Q8, um, and, uh, uh, uh, a few studies, not that many, as you know, not too many studies can be done in pediatric world anyway. But a few studies have proved that more than 15 mg of Toradol per dose and more than 3 doses per day, you're just buying more side effects. And the problem with Toradol, uh, uh, different than other nonsteroidals, especially in the kidney damage part, because, you know, nonsteroidals have three major things platelets, uh, GI, and kidney, correct? In the kidney part of the Toradol, it can be both. It can be cumulative as well as idiosyncratic. And that is the problem. And we, we did have here at Econ Children actually one kidney damage just after one single dose of high, uh, Toradol. Um-hum. So this is very significant and my dose here at Akron Children's Hospital is maximum of 15 mg q 8, and I do not do IV Toradol more than two days. If we need to give a third day, I have to revisit it and see a reason why to do it. Can I, can I interrupt you there just for a second. Cause. Yes, we did put this in our kind of parking lot for the dosage of Toradol and, and the hole that you did. So just to clarify, and, and I think this is actually part of the black box warning for Toradol is that in, in age, I think it's less than 13. I'd have to go back and read, but they're recommending, yeah, they're recommending no more than, uh, 15 mg as a single dose. Correct. Um, and so, uh, Doctor Joshi, we're talking about Toradol dosing. And kind of the recommended, uh, dose and interval and, um, questioning the 30 IVQ6. What, what is your thought on that? Or what is. So, I, Yeah, I agree with Fareed completely. Uh, in fact, we use 15 mg, uh, 3 times a day, and the, that's why it allows us to best combine, uh, uh, Tylenol with Toradol. And if, suppose someone wants to use it 4 times a day, that's fine. Then you combine 15, but still go, use 15 mg as your dose, 15 mg 3 to 4 times a day with 1 g of Tylenol, again, 3 to 4 times a day. And, and that combination will provide you significant pain relief, such that opioid consumption can be decreased by approximately 50%. Um, imagine that. So, and then add wound infiltration to that. So in most surgical procedures, you know, particularly the outpatient type of surgical procedures, you combine wound infiltration, Uh, uh, if not ketorolac for outpatient, you know, oral, um, NSAID and, and, and Tylenol, that's it. So I agree that 15 mg dose. So, so you load with 30 mg in an adult and then do 15 q6, I mean, uh, Q8, I'm sorry, Q8. Right. And, and you get the Tylenol and the Toradol together? I'm, I'm sorry. Yes. So loading would be intraoperatively, say, either, uh, you know, IV Tylenol, IV staminophenne, and then if you're using Toradol, then it would be 30 mg at the end of surgical procedure. For patients who cannot consume things. Orally, then I would use Toradol, uh, typically 15 mg, 3 to 4 times a day, depending upon the type of surgical procedures, and then IVH morphine until the time they take orally, and then move on to ibuprofen and oral Tylenol. Excellent. That, that is very, uh, uh, very similar to what we practice here. The only exception is I don't load with 30. I still load with 50. Yeah. As, as you should, yeah. Correct. Because of that black box warning. Correct. Yeah. Yeah. So. All right, we'll move on, uh, this, uh, next, this slide here, again, I think this is the third time you guys see this slide. Uh, uh, quick, quick note about Ultram, uh, or tramadol. It's a new receptor agonist. It's a very weak, uh, norepinephrine and serotonin reuptake inhibitor, but that's an advantage because that's another mechanism of action. Uh, cause sometimes you do not want to just repeat banging on the same receptor that already have shown you some resistance. Uh, then you move on to another receptor. So, tramadol gives you that extra option. And, and, and I personally found that it's an excellent, uh, choice for muscular pain. So, all, all kids with congenital, uh, scoliosis and those kind of things, because there, there is always a muscular element of the, uh, somatic, um, uh, pain that tramadol, Work very well for that. Obviously acts centrally and the good news for tramadol as of yet it's still a Schedule 4 drug in the US. It's considered opioids everywhere else, but it's a Schedule 4 drug for us, of course it has a potential for addiction. All right. So, Tylenol codeine, um. Hm. Which used to be the best option for most surgeons for a long time, at least here at Akron Children. Um, so let me just give, uh, everyone a quick update about, uh, Tylenol, uh, codeine and what's going on with the FDA, uh, and, uh, our practice here, because it's a very popular choice, especially the fact that we have it as elixir. So, codeine is a weak narcotic analgesic, and, uh, the most common formulations, Tylenol codeine, which is 120, 12, and 5 mL, and of course Tylenol 3 and 4, and it's extremely rarely used as a sole agent. Codeine has a very unfavorable side effect profile, uh, high incidence of nausea, vomiting, constipation, more, even more than the stronger narcotics. So, you compare codeine to hydrocodone or oxycodone, you get more side effects out of codeine. Uh, codeine is a Schedule 2 as a single agent, and I think Doctor Simpson mentioned that earlier. Or more than 90 mg in a unit dose even if combined, but it becomes Schedule 3 if combined with other non-narcotic drugs like acetaminophen or aspirin in very small amounts like antacids or diarrhea, anti-diarrhea syrups. It can be Schedule 34, or even 5, depending on what formula. Codeine is not a good choice of addiction, so we don't have to really worry about people getting addicted to codeine because of the unfavorable side effect with minimal tolerance, especially to constipation, while less euphoria, personal pleasure, or satisfaction. So what is the problem with codeine? Why is the FDA after codeine? It's basically the drug for mycokinetics. The conversion of codeine to morphine occurs in the liver and is catalyzed by the cytochrome P450 enzyme CYP2D6. 10% of Caucasians lack that enzyme, and we used to call them poor metabolizers. I remember the days of my training. This was the major issue of codeine that people always tell me, Well, remember, 10% or 15% of your people will not get the desired effect, and this is because they were poor metabolizers. But more importantly, this is what's coming up lately in the last couple of years, and seriously is 10 to 29% of North African and Ethiopian people have multiple copies of the gene responsible for the CYP2D6 enzyme, and that makes these people. Labeled as ultra rapid metabolizers, and these patients will end up with extremely higher serum levels of morphine after a normal dose of codeine. And the reason for that is codeine is totally dependent on conversion in the liver to morphine through this enzyme. So the dose of codeine is actually 10 times the dose of morphine. So if you give somebody 0.1 mg per kg of morphine, you give 1 mg per kilo of codeine. So it's 10 times knowing that only a small portion of it will convert to morphine. With those ultra rapid metabolizer people, then you will get 10 times the dose of morphine, uh, in those kids. Uh, The CYP2D6 has been implicated in the toxicity and death of neonates when codeine is administered to lactating mothers, particularly those with increased 2DY6, and this is reported recently. So, again, a mother taking Tylenol 3 or 4 for whatever reason and lactating, and, uh, two babies have been dead because of that. About a year ago, uh, actually a year ago tomorrow, the FDA is reviewing reports of children who developed serious adverse effects or died after taking codeine for pain relief after tonsillectomy or adenoidectomy for obstructive sleep apnea syndrome. Um, again, recently, there are 3 pediatric deaths and one non-fatal but life threatening case of respiratory depression were documented in the medical literature. You have the references there. These children were aged 2 to 5, had evidence of inherited ability to convert codeine to life threatening or fatal amounts of morphine, and all of these children have received doses of codeine that were within the typical dose, so no one was overdosing these kids. Again, now there is a larger study conducted by the FDA to review the safety of codeine to determine if there are additional cases, because people will claim that it's only after tonsillectomy for obstructive sleep apnea, but that's not the case. Those two neonates died without obstructive sleep apnea, so the FDA is looking at additional cases of inadvertent overdose or death in children taking codeine. And if these adverse events occur during treatment of other kinds of pain, such as post-operative pain following other types of surgery or procedures. So what does the FDA recommend? If prescribing codeine, use the lowest effective dose for the shortest period of time. Don't administer more than 6 doses per day, so no more Q2 to 3 hours of codeine. And then you have to counsel the parents or the caregivers on how to recognize the signs of toxicity. And consider prescribing alternatives, which is coming very soon, that actually it's not considered. It will be you must prescribe an alternative coming very soon. And there are tests for genetic CYP2D6 genotype and of course if anything happens, please report it to the FDA Midwatch. So should we change our practice? Uh we posted this question to, I don't expect anyone to read this, uh, slide here, to, uh, to the, uh, uh, list of pediatric hospitals all over the country, and the responses were 90% of the hospitals all over the country, those are the responses, uh, have already taken codeine off their formulary. So, and, uh, we here at Akron Children, we just sent out a letter. I guess you received it. Uh, it's, uh, November 1st here at Eon Children. There will be no more codeine in our, uh, uh, pharmacy here. All types of, uh, codeine, uh, uh, formularies will be taken off, and it will be taken off the order sets as well. So, same stuff. This is, um. So, what are the alternatives? Oxycodone, is oxycodone the alternative? Maybe. It's a potent narcotic. It's a Schedule 2. The good news about oxycodone, it's available as elixir for our pediatric population. Uh, it can be as a single drug, so that's another good news. It does not have to be combined with acetaminophen. Of course it can be combined. Most common forms are oxycodone, Roxycodone, those are non-combined. Roxyt, uh, of course, everybody's aware of Percocet and Percodan and Thyylox. The difference between Percocet and Tylox is the amount of Tylenol. One limiting factor is the dosing of oxycodone. It's 10 times more potent than codeine, so it's dosed at 0.05 to 0.1 mg per kg, which can be a problem for very small children. Um, again, it comes as 1 mg per mL, so you have this 6 or 7 kg, um, 9 month old baby, uh, and you want to prescribe some oxycodone for whatever reason, then you might end up giving the mother, uh, a TB syringe to, to titrate 0.2. Of the syringe and that will be the dose so obviously we started thinking that this can be a major problem as well. Some hospitals, especially Boston Child, are already discharging the mothers with TB syringes pre-filled, so they do not have to titrate anything, and they give the mother 6 or 8 or 10 of those for the next 2 days and give it every 4 to 6 hours. So that's a solution to that problem. Is hydrocodone the answer? No hydrocodone preparation without acetaminophen. We already discussed that. Uh, the good news about hydrocodone, we have Lortab as an elixir. Again, remember, I'm always thinking of pediatric mentality. I have to think of the kids. Uh, so, Elixir is available and it's widely available drug. Morphine is available also. We have it here at Akron Children for our NICU only as 0.4 mg per mL, again, to avoid, uh, the dilution and the concentration and how much of the medicine you should give to be safe. Hydromorphone is my most favorite drug, and I think Doctor Simpson will agree with me on that. Um, it's 7 to 8 times more potent than morphine. Um, it's recommended for resistant severe pain or multiple allergies or side effects with the other narcotics. It has a much better profile overall, and that's why it's our first choice here for PCAs. We do about 1000, uh, PCAs here at Akron Children per year, and 950 of those 1000 PCAs are hydromorphone. It's available as an elixir, 1 mg per mL. Don't forget that you can give a nonsteroidal, again, I think we discussed this, and because it's equipotent to codeine. So if a surgeon is totally in love with codeine and, and, and not feeling well because codeine is being taken away, you can do non-steroidal, and ibuprofen 10 mg per kilo q 6 to 8 hours in many studies for mild to moderate pain has been shown to be equivalent or equipotent to codeine also. Same thing for Tylenol or acetaminophen 10 mg per kg. Just make sure you remember the maximum dose allowed. Uh, what is the maximum acetaminophen, acetaminophen dose? I, I, I'm sorry, I have just to say this for adults. I should speak about pediatrics only, but the FDA is moving the maximum daily dose of acetaminophen from 3, I'm sorry, from 4 g per day to, down to 3 g per day. So, this patient that you give in, The OR, the Ofev IV Tylenol 1 g, you only have 2 g left for that day, so it's 3 g per day maximum. And again that should raise our attention when we prescribe Percocet or Vicodin or all those drugs that have acetaminophen in them that the total maximum dose of acetaminophen now in adults is 3 g per day. Children, the dose is 7.5 to 15, and again, young children, maximum of 60. This has been 100 mg per kg per day for years, actually for decades, um, and it just got changed recently in pediatric population to 60 for infants and late infants, if you want to call them, which is up to the age of 2. Anything above the age of 2, uh, 90 mg per kg per day is the allowed dose. Please do not forget to calculate based on lean body weight. We have, remember we have 40% obese pediatric population currently in the US, so if you have this 6 year old who weighs 60 kgs, which is again not uncommon, we see this in, in, in, in, in multiple occasions, please, please do not dose your acetaminophen or non-steroidal or opioid based on their actual body weight. Nor on their ideal body weight, so you have to know how to calculate the lean body weight for every child and base your doses based on. Remember, narcotics, local anesthetics, nonsteroidals are all very fat soluble drugs, and this will be a very good case for mortalities if you don't pay attention. Thank you very much. So that was fantastic, and you've raised a million questions. Just a million, just a million, um, and I, I invite the other faculty, Stefan, if we can bring everyone up because I, I, I have some questions here. Are you saying, can I summarize? Can I put words in your mouth here, please? I do. I send a patient home after a straightforward. Uh, I don't want to say inguinal hernia repair because I don't actually send them home on narcotics usually, but let's say I do. Hydrocodone is what I'm sending home. You said the hydromorphone comes in an elixir. What do I, I have always, I, I always use Tylenol with codeine elixir. Always. I, so what do I do now? See, we, we came up here. I don't know whether, can we show this? We. Came up here at Akron Children with a with a nice little card and I, I think I distribute it to all departments. You didn't get one of those. I usually those things usually make it to the side of my desk and I forget to look. So the alternatives here are very simple. Uh, if, uh, I would recommend pull it up and they can see it. Put it on the top of your computer there, yeah, um, like. Put it right rested on the top of your computer. Yeah. Yeah, there you go. Rest it here. So what's your summary? So what is, I would say hydrocodone should be your, again, remember we are talking about opioids, so we are talking about. Right. Pain 7 or above, correct? Right. Or maybe less than 7 if, if not controlled with acetaminophen no steroids or tramadol. OK. Hydrocodone will be my first choice. OK. Lortab, 7 1.5 and 15 mL of Lortab, 7.5 mg. So, it's good that it is only 0.5 mg per mL. So, that gives some room for less error on titrating the dose. OK. It is the best drug. So, it's a higher volume then? Correct. It, it is much better profile than, uh, is that good? Yeah, they. No? OK. Well, I have it here. If any, if anybody is, is interested, I'm more than happy to mail it or e-mail it. Um OK, so, Lortab is what you're recommending. Correct. It's much nicer profile than codeine anyway. The dose is exactly like the morphine dose. It still needs CYP2D6 to be converted to hydromorphone to act, but the good news is hydrocodone dose is 0.1 mg. So even if you have an ultra rapid metabolizer. Um-hum. While you're giving hydrocodone, you tell me it's the same problem. No, you're only given 1/10 of the dose of codeine. See, codeine, let's say the same, the child who weighs 20 kg will get 20 mg of codeine, will get 2 mg of hydrocodone, correct? The 20 mg of codeine in an ultra rapid metabolizer will convert to 20 mg of morphine, but will convert to only 2 mg of morphine. The hydrocodone will. Correct. Convert. The hydrocodone, yeah. So, so you're still, you're still safe. You're still within the range. Uh, and it, it, it's available everywhere, because one of the problems with oxycodone, which is a better, a little bit better drug than hydrocodone, but it's not available as an elixir. Yeah. Many, many pharmacies do not carry elixir oxycodone. By the way, we use, uh, elixir, particularly for some of our foregut surgery, um, right. You know, anti reflux surgery, alagia, things like that. Yeah, yeah. Well, and so, um, and then for, for inpatient IV stuff, you're saying hydromorphone. For inpatient, uh, our PCAs are hydromorphone, period. And, and, and until proved otherwise, unless we have complications, then we don't change it. Wow. And our order says it just says morphine, just when we do it. Correct, because you do the intermittent thing and you guys are more comfortable with morphine and floors sometimes are not very comfortable with hydromorphone. OK, so. But when we do it through a pump and the pen service is rounding 23 times a day. Hydromorphone. Correct. OK. Um, And so, what was the final verdict on the frequency of Toradol? I, I get the 15. Are you a Q6 or a Q8? Q8. OK. I, I do not do Q6 at all. OK. And that sounds like Doctor Joshi agreed with that as well. He, he said you could do Q6, but Q8 was your preferred. 4 times a day, yeah. Yeah. Any comments from, from the three of you, uh, virtually here, uh, on what's been said so far? Let's go to, uh, first Doctor Joshi. OK. Um, so, uh, I, a little bit about, again, I don't do pediatric anesthesia. Um-hum. So, uh, everything I say is about adults. Last time I did pediatric was 20 years ago. Um, and so, uh, uh, with that said, I'm also a proponent of hydromorphone to morphine. Um, yes, hydromorphone is a little bit more expensive, but the overall profile, not the side effect profile, the pharmacokinetic profile is far better. Um, particularly when we, you see, most of these big cases, we load them with opioids intraoperatively. And the pharmacokinetics of hydromorphone is such that if, when we, we give in small boluss to achieve, say, in the recovery room, to achieve a certain pain score. Um, um, the peak level in the CSF, or hydromorphone are achieved better, faster, in contrast to morphine. And so when we get an optimal response in the recovery room and we discharge the patient out of the recovery, we are still, we get the, you know, we don't get further increase in, in, um, Increase in CSF levels of hydromorphone, and I, I'll be happy to share, I mean, if I wish I had a presentation, I could have shown a slide here, because it's better explained on a slide. But if it's morphine, let's say I give a morphine bolus, and, and once I've achieved an optimal pain level, my last dose of morphine bolus, let's say, was 2 mg. By the time the peak level of the 2 mg occurs, the patient will be discharged from the recovery room, and then the patient will be on the floor achieving that higher peak level, causing more side effects, respiratory point of view. OK. So that's why we prefer hydromorphone. Also, I'm at Parkland Hospital in Dallas, so the type of patients we get, they have a lot of diabetics and, and Hispanics and African Americans, so they may have some renal dysfunction, and, and because of that, even if it's minimal, we try to avoid morphine. So that's why I, I, we prefer hydromorphone. Um-hum. Um, so that's combined, uh, comparing those two. Obviously, codeine doesn't come into play for us because it's more for kids. Um, Uh, so that's my take on, on the opioid part of it. Doctor Simpson, I would have to say I'm kind of impressed that you use that much hydromorphone with your pediatrics. It's been a hard sell for us. They will use morphine almost routinely in the PCAs in our pediatric population. Once in a while we even see a fentanyl in the pediatric population. Now when we start using orals, we do have an oxycodone elixir here and so we are very quick to go to that and then again schedule our acetaminophen and then just use the oxycodone elixir for breakthrough. So we use a little bit more of that. Can I, can I ask, uh, uh, Melanie, you've mentioned fentanyl in your, in your talk, and then, uh, just kind of mention that to me, um, kind of conceptually, I don't get fentanyl outside of, you know, um, an acute event, acute event, uh, maybe in the ICU around a procedure. Like that, but as a fentanyl PCA, I mean, you're just going to be in tetany pushing that button fast enough. So, tell me your thoughts about uh fentanyl. I, well, I, to be really honest, I think that we have gotten this, and I would have to say it's a false sense of security that because it's such a short duration of analgesia. It's a quick onset, so patients go, oh, you know, I'm getting something, but then we're not committed to 3 hours of analgesia, you know, that they can kind of get through it. And so for those patients who truly have, as somebody mentioned earlier, that a lot of post-op pain is very much movement related, that if they're sitting still, they're doing pretty good, you know. Again, if we've got those other things scheduled as part of their multimodal analgesia, but then when they move, if they can just get that boom and it's in and it's out of their system, we use, we kind of wax and wane, to be really honest with you. In adults we by far use the most hydromorphone and PCAs than any other of the medications. But if we have patients who have problems with morphine or problems with hydromorphone, some of our trauma patients, we routinely will start them on a fentanyl PCA because They've got severe pain because they're kind of broken or they've had lots of issues. See how much they use in about the 1st 24 hours and then we'll convert them to something longer acting once we feel like we're at a safe point with them. And, and while we're on PCA, I'm sorry, I didn't mean to, um, tell me about dosing interval. Um, you know, uh, I see dosing intervals on PCAs that seem quite long to me, and that seems to get you out of that sweet spot of that sinusoidal curve you showed, uh, Melanie. So. Um-hum. Talk, talk to me about dosing intervals, maybe for hydromorphone, for instance. Uh, well, my feeling is, you know, if they're only using 1 mL, if they're getting 0.2 mg, or if they're getting 1 mg of morphine, doing it, you know, a lot of times they'll do it every six minutes, that's OK. But if we have somebody who's had, say, more pain and they're needing more analgesia, to me it's a really, it's a safer thing if I'm going to increase them to 2 mg to lock them out at like 10 minutes because then we know that they've actually felt that first dose before they automatically hit that second one. It's kind of that built-in safety piece routinely. I will tell you, when we have patients who are on chronic opioid therapy, if they come in, you know, I, I would much rather give them a bigger dose less frequently. You know, like it's not unheard of for us to do 3 or 4 mg of IV morphine, but lock them out like every 20 minutes. And the reason behind that is when you have really small doses where people who are on chronic opioid therapy. They get so anxious because they just have to hit that button and I mean they're like seriously, you know, setting their, you know, their phone to go off so that they know exactly when to hit it because they're just getting little bits. If they get a bigger dose they feel it, they relax and they do well, but then they can't get another one until that one's really into their system and starting to show them that they're getting pretty good analgesia with it. As somebody mentioned before, I will tell you that our rule of thumb is that their demand dose always has to be equal to or greater than their continuous infusion. So, you know, for most patients, as you get into some of the palliative care situations, it's a little bit different, but for the most part we want that demand dose to be enough that they truly feel it or that they get some pretty quick relief from it. Ibrahim, I have a question, and this has been addressed, but I want to go over it in more detail. I get very confused about when I'm prescribing a, um, combined medicine such as Tylenol with codeine or, or Lortab, and saying to the patient, take Tylenol. If you need the narcotic, take it, but I'm giving them a narcotic with Tylenol. How do you prevent, uh, this seems to lead to a situation of Tylenol overdosing now. Correct. Then maybe, if that's what you like, then maybe switch to oxycodone. Right. Which can be prescribed. So, you either take Tylenol or you take. Yeah. Because it gets very confusing. Yeah. If you give the family a combined drug. Yeah. With Tylenol in it and give them all the instructions in the world. Remember, their attention span usually is, is in, in many, many areas. When I get out of the hospital, how to, how to get out, when we go there, who's going to take care of this and that, and then you are giving them the discharge instructions. I wouldn't give them a drug with Tylenol plus Tylenol alone. I wouldn't, but if that's what you like, then you give them the Tylenol alone and oxycodone, which can come without Tylenol. I mean, isn't that true for, is that an unusual, it seems to me, isn't that what most surgeons tell? I, I, there are patients that don't, you, do you not tell them to take no, because you use, uh, A Cox too. Yeah, I use a Cox too. You can do, you can do Motrin. You can do ibuprofen, right? Motrin or Tylenol. So if you want to do hydrocodone combined, then, then instead of doing Tylenol Extra, do ibuprofen extra, which way it works better, works better. So hydrocodone does not come alone just like codeine, not in the US, right? Correct. No, codeine can be alone in the US, but it's hard to find. But it's extremely hard, but hydrocodone cannot. OK. Can I just go back to the PC? Question for the dosing interval. This is one of the reasons why here we love hydromorphone. We space it every 20 minutes. Wow. So the lockout time is, is 20 minutes and, uh, we do morphine every 10 minutes, fentanyl every 6 minutes. So, if you, you are absolutely right. If you're doing a fentanyl PCA, you push it, that's what the expectation. That's why we set up the, the button to, uh, give you the lockout time every 6 minutes. So you're going to push it 10 times an hour. I like morphine 6 times, hydromorphone 3 times. Alan. Um, yeah, I like the idea of, um, that Doctor Simpson just mentioned of giving a scheduled, um, uh, non-opioid in the post-op period like uh the ibuprofen or like acetaminophen and then having an as needed uh opioid like oxycodone elixir or hydromorphone elixir in small. Quantities, but keeping that as needed and keeping them on the scheduled non-opioid and maybe even something like pregabalin or or something else, depending on how severe their pain is um scheduled, it's sort of almost like the, like you do the basal on a PCA but it's a non-opioid basal, and then they have as needed opioids, so we're trying to always kind of minimize the opioid, and I think that's a good goal um and the the elixirs, um, we have them available easily without acetaminophen, oxycodone, and hydromorphone. The Tylenol with codeine and the hydrocodone come with acetaminophen, the elixir, but the oxycodone comes without. So those are those are things that we think about. The other anecdotal point, I treat a lot of chronic pain patients, and Houston's a bit of a hub of addiction and drug problems that spill over and Oxycodone tends to be a drug that is very sought after on the streets, as is hydrocodone, but oxycodone has a very high, as they say, likability factor among drug addicts. They find oxycodone to be very Euphoria inducing and very kindling to some extent. So I just would have a little caution with oxycodone for extended periods of time or in people who have a history of drug or alcohol misuse. I think oxycodone is a bit of a dangerous drug in that population, and I know that that's not a focus of what we're sort of dealing with today, but it blends into that inevitably in some of the chronic pain patients. Is it, is it worse than hydromorphone? Um, it seems to be oxycodone seems to be kind of off the charts as far as, um, uh, likability studies, uh, go in addicts. It's probably the worst choice of opioids as far as, um, somebody with a previous history of opioid addiction or alcoholism, that kind of thing, uh, oxycodone or Percocet is probably a bad choice for that patient, much, much more likable, for example, than morphine or hydromorphone. So, I just, I gotta ask one more question about the PCA because we heard, we heard kind of uh. The 10 or 20 minutes, uh. Yeah. A lockout for the pediatric population. We heard, uh, 10 or 20 minutes from, uh, Melanie, which, uh, to me, had this kind of chronic pain component behind it. Uh, so, I'm going to have Doctor Joshi be our tiebreaker. Um, uh, well, not, not a tie, well, I guess, uh, uh, or see if he has any dissent. So, the average adult postoperative surgical patient on a PCA dosing interval, what's your opinion? So, I would like to separate out opioid tolerant versus non-opioid tolerant. Yeah, uh, let's say opioid naive. Hasn't, hasn't been traditionally taking medications. So opioid naive, if I was to use morphine, then I would start off with 1 mg every 5 to 6 minutes, or, uh, or, or 2 mg every 10 minutes. If I was to use hydromorphone, which is what we are going to, 0.2 mg every 10 minutes. So that's the starting point for opioid, uh, naive patient. For the opioid tolerant patient, You know, we uh, we tend to use the higher dose for a start. And obviously, as was emphasized by Melanie, cannot emphasize enough, we've got to give their daily dose, at least half of their daily dose pre-op. And then maybe in this patient population, think of a background infusion, but not for a start, just. As a backup, but early, early addition. So that's our, our approach for PCA. Hey Brian, I'm an old anesthesiologist too. I, I need a vote on this. I didn't mean to exclude you, Eleanor, of course. I think you think 7 to 10 minutes for an interval is, is great for just about everybody, every drug across the board. Yes, OK, it's a good roundup, yeah, so I, I do want to go, uh, Doctor Joshi, you, you wanted to talk for a second about, um, dexamethasone and the other stuff that you had mentioned. So I want to give you the floor in 1 2nd, but before I get to you, I wanna answer, I want to address Laurie Compton's comment. Which basically was the summary of what we had concluded is the whole idea of ibuprofen using a combined Tylenol, uh, codeine, or hydrocodone, um, for breakthrough. I would love to see, and you might all know, and this seems like a basic question, but has someone looked at the use of, of COX-1, uh, solutions and because in, in adults you don't need it because you can use your CX-2s, but in, in peds, we can't. So we're talking about using ibuprofen or Motrin. Um, and the question is, is there, do we see higher bleeding complications in those patients, and, um, you know, because I don't routinely prescribe it, and I probably should, um, especially, so we, we should probably do a prospective trial comparing Tylenol to ibuprofen as the maintenance with, with this as a breakthrough and to see if there's a difference because if not, that seems to be the obvious solution. I, I can help you to answer this question. Uh there was always a question about tonsillectomies, as the rate of post-tonnsillectomy bleeds about 1 to 2% in the best hands, and this was a, uh, a clear reason for should we give or should we not, and it was a crime to give a non-steroidal. Like if I give an intraoperative dose of Toradol to a, a TNA case, then, then I'm in trouble. And uh at least 3 or 4 huge studies, at least 1000 patients in them, and the latest was done by the Cleveland Clinic that showed absolutely efficacy and safety of giving non-steroidals to post TNA cases. So if, if you, if ibuprofen is safe from the bleeding point of view after tonsillectomy, it's absolutely safe for your hernia repair. Or, or, or, uh, or mass excision or whatever. Yeah, I mean. I mean, and I didn't want to misinterpret the CX one and CX two with my little bar graph there. OK. They can have both effects. Right. It's just more. What's the I. understand. But you're, and actually, Toradol has more than ibuprofen. So, you're probably, You know what I mean, right, and I give those to, yeah, intraoperatively, and the same kind of, uh, literature came out of the prostate, uh, prostatectomy world using to, which is another bleed, bloody blood, and I don't ever get blood loss, so I'm in a great situation. Uh, like most surgeons, like all surgeons, like all surgeons, at least not audible, right, yeah, yeah. So, uh, Doctor Josie, go ahead because I think this is something that I've actually always wondered about because I have absolutely no idea how to use these augmenting drugs. So yeah, both dexamethasone and IV lidocaine, we want to hear about that. OK, so first I'll start off with the easy one, which is dexamethasone. Um, I believe that, uh, one single dose of, um, and believe based on good literature, good, uh, systematic reviews, um, that 4 to 8 mg of dexamethasone, single dose given intraoperatively after induction of anesthesia, Has significant beneficial effects and should be used in most patients unless there's a, a contraindication. Um. And, and that provides good antiemetic prophylaxis, as well as good pain relief and elation in the postoperative period. So that's with dexamethasone. Now one of the questions commonly asked, sorry, there was a question. No, no, I don't want you, I don't want you to leave this topic. So when you're done, I want to ask a question. So if you're still talking about dexamethasone, keep going. Yes. Yes. So one of the questions commonly asked with dexamethasone is, oh, I have a diabetic patient, and, and, and, you know, do I not use it? Is that a contraindication? And the answer is not in a, a diabetic who's well controlled. Um, there is no question that even 4 mg of dexamethasone may increase blood sugar levels. But the current recommendation by the American, uh, Diabetic Association and American, Uh, College of, uh, Endocrinologists is that you treat blood sugar levels in the perioperative period, only if they go about 140 to maybe 180. So when we looked at these data, there were, 6 large studies looking at blood sugar levels and, and dexamethasone, and yes, they did increase blood sugar levels in diabetics, but it never went above the, uh, treatment threshold. And therefore, we believe, even in, in well controlled diabetics, it's, it's actually a good drug. Then we also looked at, we being the prospect group again, we looked at, um, uh, the, uh, patients who are at high risk of infection, preop infection. And, and found that one single dose did not increase, uh, the perio infection. So with all that said, uh, I believe that dexamethasone should be a part of that multimodal analgesia technique in most patients, same as an NSAID or a COX-2, plus a staminophhane. So, uh, a comment and a question, um, I, I am very open to giving dex, um, for any of my patients if, if, if, for, you know, you worry about wound healing. If my anastomosis can't handle one dose of dexamethasone, it's a technical error. Um, I don't think that, that, that's gonna attribute to, uh, anastomosis breakdown or, or, or, or closing of the abdominal wall. I don't think I would be shocked if it was. But are you saying, you said. I think you said all cases unless there's a contraindication, even a simple ditzel case, you give dexamethasone. Are you talking about only major surgery? No, even, even out, in fact, the benefits are more for outpatients, uh, particularly, you know. Uh-huh. Because they're going home, they have high incidence of postop nausea, vomiting. They, they get Lortab, Lorcet, Vicodin type of stuff, so dexamethasone really helps. So, uh, in fact, I believe that the majority of the patients would benefit, uh, whether inpatient or outpatient, from one single dose of dexamethasone. We're going to study it in kids if it hasn't been looked at already. Alan, did you wanna make a comment? I saw. Yeah Sorry, no, just to reinforce exactly what Jiff said that, um, and I think at MD Anderson they've got, they've begun to give every single surgical patient dexamethasone with induction. Wow, OK, with induction, yeah. Does it, it doesn't, does it matter when you give it? Good question. After, immediately after induction. So I was actually speaking at MD Anderson as a visiting professor last month, and, and. Um, have emphasized that, and I, I, I understand they're routinely using it, same as what we have been doing it now for our, in fact, Henry Kellet visited MD Anderson just a week before I did. Um, again, emphasizing, so it was kind of double whammy for MD Anderson. Um, and if it's an airway case and they want to give Decadron, there's a, you can't now. Why? You can, uh, in fact, so I want to separate out airway cases versus pain relief. Um, now, if you want to decrease, uh, uh, edema for airway cases. I, I would use 8 mg of dexamethasone, because for reduction of, uh, edema, you want a slightly higher dose. Uh-huh. But for pain relief and PONV prophylaxis, 4 mg is adequate. I see. So, it's just a difference of the, OK. So, you would give additional dose. Yeah, there, there are three doses, one for pain, one for nausea and vomiting, one for anti-inflammatory action, which, Is the airway edema and that. So you just add more. You, you gave your, your induction dose and you say, you know, there was, we did a lot of instrumentation. We're going to give another 4 mgs now. Well, what, what I, what I personally do is the dose for nausea and vomiting is 0.15 per kilo. The dose for pain, if I give it for pain, 0.1 per kilo. If I give it for anti-inflammatory action, 0.5 per kilo to a maximum of 8. I see. That was huge. I did not know any of that. To a maximum of 8. So, all, all our direct laryngoscopy cases, failed extubation cases, all these kind of cases. Right. Right. Get 0.5 mg per kilo. OK. Uh, I, I want to. Yeah. Hear, just, I know we have a few minutes left, but I want to hear a little bit about IV lidocaine. Cause that was another thing mentioned. And then I want to clarify this maximum dose of Tylenol because, uh, what, what I presented is different from what you're saying and I want to make sure our audience gets this clear. So, Uh, maybe we can start with the IV lidocaine thing and then, uh, OK. And then do the Tylenol. So IV lidocaine is now called a poor men's epidural analgesia. Um, the dose of, uh, IV lidocaine, um, as an infusion, never a single dose. You start off with 1 mg per kg infusion and then follow it with 1 to 2 mg per kg per hour. Um, and, and, uh, that has been compared in abdominal surgical procedures, um, with epiduralalgesia and shown significant benefit with pain relief, but more importantly, with time to return to daily living, sorry, time to return of bowel function. And and ambulation and hospital stay. So, our prospect group recommends use of IV lidocaine infusion, but not primarily as a first line of therapy, only as a backup when, uh, if a patient needs to undergo thoracic surgery or upper, major upper abdominal surgery, where we would use thoracic epidurals, and, uh, either there's a contraindication to thoracic, Or did not work, then I would resort to IV lidocaine infusion. Or if I have a patient undergoing, even if it's a laparoscopic procedure, but, um, say, has significant renal problems, I can't use, uh, an NSAID or a COX-2, as well as has liver issues, so I cannot use the temnohane, then I would use IV lidocaine. Uh, why are we recommending, uh, as a secondary, second line of therapy, not the first, though, there is good data with efficacy, is because the dosing still remains fairly controversial. And yes, there is, uh, there are several large studies done, but the dosing used in each of these studies is so much variable that you cannot come to a consensus to dosing. The dose I just mentioned is one of the, um, kind of balance between the extremes. Um, and, and so that's the only reason why we're holding back on, on, on, on IV infusion of lidocaine. Otherwise, it just, it has anti-inflammatory properties. Uh, I know, Brian, you just mentioned, uh, in your presentation, anti-inflammatory. You mentioned lidocaine and you took back, but actually, lidocaine IV does have anti-inflammatory properties as well. Yeah, yeah, great. Tylenol. Yeah, I, we got to clarify, cause you, cause, uh, I had put up a graph which was from a package insert, actually, that says for adult, 1000 mg IV q 6 hours. Correct. Which would get us, which was, you're saying was old. Correct. Old news. New news is, Grams max per day now I actually just had a conversation, I would say 2 months ago or 3 months ago with the head of the anesthetic and analgesic, uh, uh, drug product advisory committee. It's AAD PAC. It's part of the CDER, the Center for Disease, uh, from the FDA, and, uh, uh, this group was assigned to deal with, uh, uh, both the Tylenol toxicity, uh, issues, which, which is about 35,000 cases a year. In the US gets liver damage from Tylenol 35,000 cases as well as they are dealing with the codeine issue and the hydrocodone issue, um, codeine because of the enzyme, hydrocodone because of the addiction. So, those are three major tasks and one of the major things. Was to reduce Tylenol down from 4 to 3. And my understanding, it's already going. It's in process right now that the Tylenol will only be 3 g per day, will not be 4 g per day anymore. And Doctor Joshi, that's your understanding? Uh, so, I want to clarify that. So, because there's so much confusion and, and obviously, I beg to differ from, Um, um, so a little bit of background here. Historically, as we all know, the, uh, the recommendation from the FDA is no more than 4 g per day of, of Tylenol. Then, uh, last year or year before, uh, J and J, which are the manufacturers of Tylenol, went to the FDA and, and, uh, manufacturer of, of any company, um, of a drug has the ability to go to the FDA and request for a change in package insert. So they went to the FDA and requested that the package insert be changed to 3 g per day. And, and, uh, that's because of the request from GNJ. Having said that, if you look at the package insert of IVF temnohane, um, it still says 1 g 4 times a day, and that is 4 g, obviously, 4 g a day. And, and, uh, the FDA has not mandated that that be changed. So the controversy is, Whether the company goes and asks for a change or the FDA mandates. The, if the company goes and asks for a change, the FDA will grant it, you know, but it will not then mandate that same change on other, um, uh, drugs, such as the IV esteminophen. So that's where the controversy lies. Tylenol only. Tylenol, the company the name Tylenol, yeah. OK. Correct. Correct. Tylenol only. Yeah. Not the IV formulation of, of, uh, esttemnophane. That still remains. So overall, temnophe safety point of view, still, uh, and, and efficacy also, because remember, we said esttemnophen has a, has a ceiling effect and no more than 1 g of dose at, and, and, Uh, because of his pics 4 times a day. So, um, for Tylenol only, there is a 3 g per day limitation, but other acetaminophen, even if you go over the counter, you will not see that kind of limitation, which is absolutely correct, Dr. Joshi. I agree with you on that. The only thing I will add is it's my understanding is that the AADPAC committee is working on making it universal for all. Acetaminophen, Tylenol or anything, and that is the expectation. It's the same group also that's dropped the level for pediatrics from 100 mg per kg per day to between 60 and 90, and it's the same group also that will demand, and that's expected early next year that no more than 325 mg of acetaminophen in any combined narcotic. All these changes are expected to be implemented at the beginning of 2014. So the 3 gs, the 60 to 90 for kids, and, uh, all combinations. So, Percocet, Vicodin, Tylox, all that stuff, uh, maximum 325 per pill, uh, of, uh, uh, Tylenol. Correct. It's actually the combination drug which have caused most harm. The patients really don't understand that they're taking more than 4 g per day. OK. Um, but, um, yeah, we'll see what, what comes out of this, but at least for now, um, uh, until the time we get, uh, new FDA rules. Um-hum. Um, the 3 g per day applies only to Tylenol, not to estteminophen as such. Um OK. Right. Well. Yeah. This was awesome.