Episode 344: Allergic Response

[SPEAKER_00]: Hello and welcome back to Agrex, I'm Jed Wolpa and today we're going to go through a high yield topic, a lot of testing comes from this and it's also a good thing you know, obviously for clinical practice too and that's going to be allergic response. [SPEAKER_00]: We're going to talk about allergic response.

[SPEAKER_00]: Now, obviously a lot of the questions that come up around anaphylaxis, but there's a lot more here too. [SPEAKER_00]: Some of it gets back into the kind of basic immunology from medical [SPEAKER_00]: but that can be tested too. [SPEAKER_00]: So we're going to go through a good solid review.

[SPEAKER_00]: All right, so let's start with just some kind of basic immunology principles. [SPEAKER_00]: So we know the immune system protects the body from foreign antigens and it does that by trying to remove them. [SPEAKER_00]: It can remove them by causing them to be destroyed by trying to contain them in a variety of different ways.

[SPEAKER_00]: Now, the obvious question, of course, is, well, what about all the molecules that belong in the body, the self, and those self molecules, the body has a system to tolerate those, it's called self-tolerance, and as we know when that goes awry, that's where we get auto-immune diseases. [SPEAKER_00]: Cell mediated immunity?

[SPEAKER_00]: is one of the two types of immunity. [SPEAKER_00]: So there's cell mediated and then a humoral immunity. [SPEAKER_00]: Cell mediated, mediated, involves, of course, immune cells directed at the elimination or destruction of pathogens or of foreign cells. [SPEAKER_00]: And the way to remember that, of course, is that cell mediated immunity is involving these cells themselves.

[SPEAKER_00]: Whereas humoral immunity, it's not cells. [SPEAKER_00]: It's [SPEAKER_00]: things like antibodies and proteins like complement that can cause cell injury and destruction of antigens. [SPEAKER_00]: But through the humoral response, the things like antibodies and other protein mediators can cause cytokines, chemokines, and things to be released, which will bring immune cells to the site of injury or infection, which leads to further response, fever, increased [SPEAKER_00]: Now, the antigens themselves that are being attacked, they can be molecules that stimulate an immune response, sometimes polypeptides like prodomine or large macromolecules like dexterans can be complete antigens by themselves.

[SPEAKER_00]: They can produce a response by themselves, but most drugs that we give are actually small, and in order to become an antigen, they have to bind to a circulating protein, and then that, [SPEAKER_00]: complex that is formed will be a monogenic, that will now be an antigen, and so those drugs are called haptons, so that's a word to remember, hapton, HAPTE and hapton, and that drug in and it's out that hapton in and of itself won't cause that immune response, but when that hapton binds to a circulating protein, now it can be an antigen.

[SPEAKER_00]: All right, let's talk about T cells. [SPEAKER_00]: So T cells have receptors which are activated by binding with a foreign antigen, and they secrete mediators that regulate the immune response. [SPEAKER_00]: We have a few different types of T cells, so we have helper T cells, suppressor T cells, and then cytotoxic or killer T cells.

[SPEAKER_00]: Now, cytotoxic cells, cytotoxic T cells, they will actually destroy things like micobacteria, fungi, and viruses. [SPEAKER_00]: They're very similar to another type of cell we have, which is a natural killer cell. [SPEAKER_00]: But this is a little different because natural killer cells don't need a specific antigen for stimulation, whereas cytotoxic T cells do.

[SPEAKER_00]: Now they both play a role in defense against tumor cells and transplant rejection. [SPEAKER_00]: This is something that might show up on an exam question, where they may ask what the difference between a natural killer cell on the cytotoxic T cell is. [SPEAKER_00]: And the key there, again, is the cytotoxic T cell is specific.

[SPEAKER_00]: It's been in a way built to recognize a specific antigen and attack it, whereas natural killer cells are maybe you could think of them as a little dumber. [SPEAKER_00]: They are just generically going to attack certain things, but they haven't been designed for one specific antigen. [SPEAKER_00]: B cells on the other hand are lymphocytes, they're a lymphocytes cell line that differentiates into specific plasma cells that make antibodies and they're influenced by helper and suppressor T cells.

[SPEAKER_00]: So there's that interchange between the T cells and the B cells [SPEAKER_00]: That the helper and suppressor T cells will help influence which B cells exist in which antibodies are made. [SPEAKER_00]: So let's talk about antibodies. [SPEAKER_00]: Their specific proteins, they're called immunoglobulins, and they recognize and bind to a specific antigen.

[SPEAKER_00]: They have something called a FAB FAB Fragment that binds the antigen and then FC, big F, like Frank Little C, like Charlie, and FC Fragment that is unique to the class of immunoglobulin. [SPEAKER_00]: So we have IGG, IGA, et cetera. [SPEAKER_00]: In fact, we have five different kinds of immunoglobulins humans do.

[SPEAKER_00]: We have IGG, IGA, IGM, like Mary, IGD, like David, and IGE, like Edward. [SPEAKER_00]: So those five are the types that we have, and the FC fragment is what differentiates the different types. [SPEAKER_00]: Now you've heard, I'm sure, of lots of different ways that we're using these. [SPEAKER_00]: So for example, therapeutic...

[SPEAKER_00]: drugs, things like ed6amab, are based on fab fragments, which allows them to bind to something because it's the fab fragment part that's going to do the binding to antigen, and so they've used this to create these drugs. [SPEAKER_00]: So in the case of ed6amab, it will bind to the platelet 2b3a receptor.

[SPEAKER_00]: So that fab fragment will bind it to that receptor as if it was the antigen it was designed to bind to. [SPEAKER_00]: When an antibody or complement for that matter binds foreign cells, that's called obsenization. [SPEAKER_00]: And it's kind of think of it as like surrounding it. [SPEAKER_00]: And it helps the effector cells then identify and kill that antigen.

[SPEAKER_00]: All right, so let's move on to those effect ourselves. [SPEAKER_00]: These are things like monocytes, neutrophils, which, of course, are also called PM ends, that stands for Polymorpha, nuclear, and Eosinophils. [SPEAKER_00]: So monocytes should be easier, remember, they can become macrophages, which actually can ingest antigens, and so both start with AM, of course, monocite macrophage.

[SPEAKER_00]: PMNs are neutrophils are really the first to appear, and they're really substances like free radicals that can help kill microbes. [SPEAKER_00]: Eosinophils are a little bit more mysterious. [SPEAKER_00]: They're clearly involved with parasites and also tumor and allergic reactions, but exactly how they work is still being investigated.

[SPEAKER_00]: Baseophils [SPEAKER_00]: are a lot like mast cells, but slightly different. [SPEAKER_00]: They have IGE receptors, just like mast cells do. [SPEAKER_00]: And then, of course, mast cells are tissue fixed. [SPEAKER_00]: So they are in tissues, and the key things to remember about them, they're really IGE dependent.

[SPEAKER_00]: They have IGE receptors, and it is byactivation of those IGE receptors, that most commonly, they will release their mediators. [SPEAKER_00]: And those mediators are involved in immediate hypersensitivity responses. [SPEAKER_00]: And we'll talk about that more in a minute, but mass cells are going to come up a lot on tests until you want to know that they are tissue fixed, that they're activated through IDE receptors, and that they release a lot of inflammatory mediators.

[SPEAKER_00]: And we'll talk a little bit more, as I said. [SPEAKER_00]: Proteins are involved in this a lot too. [SPEAKER_00]: So you have cytokines and inner lukens. [SPEAKER_00]: Those are made by macrophages, kind of a second messenger. [SPEAKER_00]: So you've got things you've heard of, IL-1, TNF, that's tumor necrosis factor.

[SPEAKER_00]: These things are part of what causes fever, hypotension by leading to vasodilation. [SPEAKER_00]: All right, and so these are interlukens and cytokines. [SPEAKER_00]: Compliment is something that comes up a lot. [SPEAKER_00]: So complement proteins bind to an activated antibody. [SPEAKER_00]: and then other complement proteins and cell membranes.

[SPEAKER_00]: And by binding to, for example, the cell membranes of bacteria, they help increase the adhesion of killer cells and antibodies to these antigens, which can lead to cell lysis. [SPEAKER_00]: So, complement are kind of like a helper protein that can help other things do their job. [SPEAKER_00]: What's important to note too, because compliment comes up a lot on tests and also compliment inhibitors.

[SPEAKER_00]: And the reason this comes up a lot is because there is a very important disease state that we talk about a lot of the anesthesia of hereditary or acquired angioidema. [SPEAKER_00]: So angioidema can be either hereditary or acquired. [SPEAKER_00]: And what's really important to note is it's a deficiency, not in compliment, and it's also not too much compliment, it's actually a deficiency in the inhibitor.

[SPEAKER_00]: of the C1 complement system. [SPEAKER_00]: So it's a deficiency in C1 esterase. [SPEAKER_00]: Now the key there is that it doesn't say, you're not going to get on a test question that is going to say complement inhibitor. [SPEAKER_00]: It's just going to say C1 esterase. [SPEAKER_00]: It may say C1 esterase inhibitor, but it might just say C1 esterase.

[SPEAKER_00]: You have to remember that it's that esterase that can cut the ester bond of complement to deactivate it. [SPEAKER_00]: And when you don't have enough C1 esterase, either because you've acquired that deficiency or because you have a hereditary cause of C1 esterase deficiency, that's what leads to angioadema either hereditary or acquired.

[SPEAKER_00]: And that's something we need to pay a lot of attention to. [SPEAKER_00]: So it's not that complement... [SPEAKER_00]: isn't working or is working too much directly, it's that you can't inhibit. [SPEAKER_00]: You don't have the normal inhibition of the complement system, and that's what leads to overactivity of complement, which can cause that tissue binds to that tissue in the airway and can cause that airway swelling.

[SPEAKER_00]: programming can cause complementive activation, which one of the big things we worry about with programming is a cute pulmonary vasoconstriction. [SPEAKER_00]: And that is, again, thought to be have a variety of possible mechanisms, but one that we do know happens is, again, that complemented activation, which actually leads to release of thromboxane, [SPEAKER_00]: And you may see a question about this because for some reason, they love to test these prodomine reactions, this prodomine causing severe pulmonary viso constriction, maybe leading to right heart failure.

[SPEAKER_00]: And so if they ask how that happens, because they do like to ask things like mechanism of what's the mechanism of, even though that probably what's most important for you to know is how to deal with it, but what they are [SPEAKER_00]: asking more commonly or at least commonly is what's the mechanism and again that mechanism you want to know that it involves compliments so a potential answer choice might be complement activation or a potential answer choice might be thromboxane that it acts through thromboxane release.

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[SPEAKER_00]: We rely on Truelearn for our test prep, and I recommend you do the same www.truelearn.com and use code ACRAC. [SPEAKER_00]: All right, let's talk about the types of hypersensitivity reactions. [SPEAKER_00]: So also, we can think of these as allergic reactions, but there's these four types.

[SPEAKER_00]: We all had to learn this, of course, in medical school, and it can come up sometimes on tests as well. [SPEAKER_00]: So type one is the anaphylactic or also known as the immediate type hypersensitivity reaction. [SPEAKER_00]: And there's a few key things to know about this. [SPEAKER_00]: This is of course going to probably be the most highly tested one because it's anaphylaxis.

[SPEAKER_00]: And that's what they really want you to know. [SPEAKER_00]: So you need to know that mediators are released from mast cells and basophiles during this type of reaction. [SPEAKER_00]: And it is after an antigen binds to the IGE antibody on their membranes. [SPEAKER_00]: Types of reactions include, of course, the famous Anaphylaxis.

[SPEAKER_00]: And then there's also things like extrinsic asthma and allergic rhinitis. [SPEAKER_00]: It does not rely on complement activation. [SPEAKER_00]: So probably the most highly tested things here are one. [SPEAKER_00]: It involves mass cells and basophils. [SPEAKER_00]: It involves IgE activation.

[SPEAKER_00]: On the membranes of those mass cells and basophils, and it does not involve complement activation. [SPEAKER_00]: So those are things that you may see come up on test questions. [SPEAKER_00]: high-per sensitivity reactions are antibody-dependent. [SPEAKER_00]: Also known as cytotoxic reactions, they're mediated usually by either IGG or IGM antibodies against a specific antigen on foreign cells.

[SPEAKER_00]: And then the damage comes from either direct cell lysis after complement activation. [SPEAKER_00]: increased attack by macrophages or killer T-cells. [SPEAKER_00]: Examples of this include ABO incompatible reactions, drug-induced immune, hemalytic enemia, and happen-induced thrombocytopenia.

[SPEAKER_00]: These are all antibody-dependent cytotoxic reactions, and that's a type two hypersensitivity reaction. [SPEAKER_00]: type 3, immune complex reactions. [SPEAKER_00]: So this is where you have circulating antigens and antibody that bind together and they form an insoluble complex that then deposits in tissue, usually in vascular.

[SPEAKER_00]: And you get complement, activation, and you get PMNs coming. [SPEAKER_00]: And examples of this include serum sickness after maybe snake, anti-cera, [SPEAKER_00]: and immune complex vascular injury. [SPEAKER_00]: The big thing to remember here for Type 3 is that it's immune complexes. [SPEAKER_00]: So these immune complexes form and deposit in tissue.

[SPEAKER_00]: And then Type 4 is delayed hypersensitivity reactions. [SPEAKER_00]: And this is probably the second most tested. [SPEAKER_00]: So Type 1, the anphalactic most tested, type 4, the delayed hypersensitivity probably the second most tested. [SPEAKER_00]: And what happens here is anogen lymphocyte binding leads to generation of cytotoxic t-cells.

[SPEAKER_00]: usually manifests in 18 to 24 hours, peaks somewhere between 48 and 80 hours, and the disappears after 72 to 96 hours. [SPEAKER_00]: And examples of this include tissue rejection, graph versus host disease, contact dermatitis, like poison ivy, and of course tuberculin immunity. [SPEAKER_00]: So when you get a TB test placed intradermally, that's what it's looking for, is that delayed hypersensitivity reaction.

[SPEAKER_00]: And because it's delayed, that's why you have to come back, [SPEAKER_00]: two or three days later to have it read. [SPEAKER_00]: So this should be easy to remember for that reason that these are things that take time for those cytotoxic T cells to develop to migrate to the location and to cause the reaction.

[SPEAKER_00]: All right, let's talk about intraoperative allergic reactions. [SPEAKER_00]: So the risk of a perioperative anophilactic reaction is very low. [SPEAKER_00]: It's somewhere between about 1 in 4,000 to 1 in 20,000. [SPEAKER_00]: The mortality is about 4%, but there's another 2% that survive only with this kind of severe brain damage, and so obviously that's not ideal.

[SPEAKER_00]: So it's not a good thing, obviously. [SPEAKER_00]: More than 90% of allergic reactions from IV drugs that we give during anesthesia occur within five minutes. [SPEAKER_00]: So while it can be delayed, it's usually pretty immediate. [SPEAKER_00]: The most common life threat in the manifestation is circulatory collapse from basal dilation and then loss of venous return leading to cardiac arrest.

[SPEAKER_00]: As I said before, anaphylaxis starts with IGG antibodies which bind antigen. [SPEAKER_00]: You have to have a prior exposure to that antigen or a similar antigen so that the antigen specific IGE is present on the surface of mass cells. [SPEAKER_00]: And I should have said this before when we were talking about the things that are highly testable about anaphylactic reactions that those type one hypersensitivity reactions is you have to be pre-sensitized.

[SPEAKER_00]: so you have to have an initial sensitization. [SPEAKER_00]: Now the thing is that patients often don't remember or know that they had an initial exposure and so you can't count on that. [SPEAKER_00]: But for the actual path of physiology, you do have to have that first exposure, which [SPEAKER_00]: probably won't have any symptoms, so you have to have that prior sensitization, which is what will produce those IGG antibodies specific to that antigen, which will then be on the surface of mass cells and Bayes of Fills so that the next time around that antigen will cross-link those IGG antibodies on the surface of those mass cells and cause their degradulation.

[SPEAKER_00]: So when that re-exposure happens, and those two IGG antibodies on the mass cells or on the base of fills are cross-linked, they will then release the inflammatory mediators, and that's what leads to bronchospasm, vasodilation, hypotension, or decaria. [SPEAKER_00]: airway swelling, etc.

[SPEAKER_00]: So what are the mediators that are involved in this? [SPEAKER_00]: So histamine is a big one. [SPEAKER_00]: There's H1, H2 and H3. [SPEAKER_00]: They contribute to vasodilation through the activation and release of nitric oxide. [SPEAKER_00]: There are peptides. [SPEAKER_00]: So there's something called eacinophilic chemotactic factor of anaphylaxis, ECF-A.

[SPEAKER_00]: And that brings in eacinophils. [SPEAKER_00]: There's also [SPEAKER_00]: You've got arachidonic acid metabolites, so lukotrines and prostate glands, which produce bronchoconstriction, vasodilation, coronary vasoconstriction, and myocardial depression. [SPEAKER_00]: You've got kindens, so small peptides and mass cells and basophils that add to this whole inflammatory cascade.

[SPEAKER_00]: And then you've got platelet activating factor, which aggregates and activates platelets, and maybe also has involved in bringing in other leukocytes to release inflammatory products. [SPEAKER_00]: I don't think those mediators, other than histamine, those specific ones, other ones are going to be all that testable, but just so you're aware in case you hear them that you've heard them once before.

[SPEAKER_00]: recognition of animal access. [SPEAKER_00]: So exposure in a sensitized person usually produces pretty immediate effect, but it can be delayed, can be delayed by 10, 20 minutes, sometimes even more. [SPEAKER_00]: Sometimes you get mild symptoms, and sometimes severe, and obviously because they have to have that prior exposure, that's important, but they, as I said, may not know they've had it.

[SPEAKER_00]: There are other pathways that can produce the same clinical picture without being anaphylaxis. [SPEAKER_00]: And in some ways, these used to be called anaphylaxtoid reaction so that term is kind of fallen out of favor. [SPEAKER_00]: Compliment activation, either via immunologic, so that's antibody mediated, also known as the classic pathway, or non-immunologic, which is the alternative pathway, can produce C3A and C5A.

[SPEAKER_00]: These are complement products that are called anaphyletoxins. [SPEAKER_00]: They cause release of histamine for mass cells and baseophils, but it is not through the IGG activation. [SPEAKER_00]: It is not anaphylaxis. [SPEAKER_00]: It's directly caused by the complement. [SPEAKER_00]: Compliment aggregation and activation and PMN aggregation are thought to produce clinical effects of transfusion reactions, pulmonary phase of constriction after proteamine, ARDS and septic shock.

[SPEAKER_00]: So, again, key there to remember, complement, [SPEAKER_00]: can produce some of these same reactions that an antibiotic reaction would, things like the pulmonary visor constriction you see after prodomine, which is not actually an anaphylactic reaction when it happens that way. [SPEAKER_00]: It's a complement mediated reaction through, as I said before, the release of Theron Boxing.

[SPEAKER_00]: There are drugs that can cause histamine release without antibody, by causing mast cells to release histamine. [SPEAKER_00]: So atracurium is a great example. [SPEAKER_00]: Atracurium can cause histamine release, but it doesn't do it by activating the IGG on the mast cell service. [SPEAKER_00]: It just can actually cause those mast cells to release the histamine.

[SPEAKER_00]: So atracurium is probably the most famous example. [SPEAKER_00]: Rockeronium and Vecoronium have very little risk for this, [SPEAKER_00]: When you hear a test question on this, it's often going to be getting at, do you know that aturcureum is high risk? [SPEAKER_00]: How about treatment?

[SPEAKER_00]: So this is probably one of the most highly tested as it should be topics here. [SPEAKER_00]: So the first thing you want to remember is stop giving the antigen. [SPEAKER_00]: So if you're still giving it, stop. [SPEAKER_00]: Don't give it any more. [SPEAKER_00]: If you can identify what the antigen is.

[SPEAKER_00]: Airway protection is key because this often will lead to the loss of an airway and you don't want to wait. [SPEAKER_00]: And hypoxemia from the Bronco constriction. [SPEAKER_00]: So you want to give a hundred percent oxygen. [SPEAKER_00]: Stop your anesthesia, right? [SPEAKER_00]: You have somebody who is getting more and more hypotensive from an anaphylactic reaction.

[SPEAKER_00]: You do not want to still be giving them seval fluorine. [SPEAKER_00]: you're going to need intervascular volume expansion because they get very leaky and a lot of their intervascular volume will both pull when they get phasodilated but also leak out of the vasculature and then of course the most highly tested thing in this whole topic is that the treatment for antiflexus is epinephrine and so if they're still [SPEAKER_00]: are not in cardiac arrest, so they still have a pressure, even if it's hypotensive, you want to start with doses of epinephrine of about 5 to 10 mics, IV.

[SPEAKER_00]: And this is sometimes tested too. [SPEAKER_00]: You do want to give IV epinephrine when you have an IV in a patient, which we always will in the operating room. [SPEAKER_00]: So, this is different than someone having an anaphylactic reaction at home or at school where they're going to do I am injection through an epipen.

[SPEAKER_00]: This is talking about people who are in the operating room, they have an IV, we are going to give them IV epinephrine, five to ten bikes at a time. [SPEAKER_00]: Obviously, if they progress to cardiovascular collapse and cardiac arrest, we would then use full code doses of a milligram of epinephrine.

[SPEAKER_00]: than the secondary treatment. [SPEAKER_00]: So you want to give anti-histamines, and it's really the H1 blockers that are important, and you think about diphenhydramine as your go-to, or Benadrill as it's often known in the United States, but diphenhydramine is the generic name. [SPEAKER_00]: And you're going to give about a half to one milligram per kilogram of diphenhydramine to get that H1 blocking ability.

[SPEAKER_00]: Then you want to think about vasopressor drips. [SPEAKER_00]: So again, epinephrine can be run as a drip. [SPEAKER_00]: If you for some reason don't have epinephrine or can't run it, then no epinephrine is probably reasonable. [SPEAKER_00]: But epinephrine should be your drug of choice.

[SPEAKER_00]: And you're going to start about 0.05 Mike's Procula Permanent and titrate from there. [SPEAKER_00]: bronchodilators, so albuterol, terbutylene, anti-colonurgics like inhaled a protropium, especially for patients on beta blockers, where the beta agonists may be competed with those beta blockers using an anti-colonurgic like a protropium may be particularly helpful.

[SPEAKER_00]: Remember, beta blockers are not a good thing for these patients, certainly not part of the treatment. [SPEAKER_00]: Steroids are very good. [SPEAKER_00]: You can give 0.25 up to 1 gram of hydrochordasone or 1 to 2 grams of methyl prednisolone. [SPEAKER_00]: Maybe better actually to give methyl prednisolone in the setting of a complement mediated reaction.

[SPEAKER_00]: You may not know that at the time, but methylpregniz alone has some action that is helpful in specifically complemented mediated reactions. [SPEAKER_00]: But whether you choose hydrochordesone or methylpregniz alone, steroids are a very important part of this treatment. [SPEAKER_00]: Even though the effect can be delayed by 4 to 6 hours, it's still very helpful and can help prevent that second phase reaction, which can recur 12 to 24 hours later.

[SPEAKER_00]: So you're always worried about that and that is why these patients have to be admitted to an ICU for at least 24 hours because they can have that recurrence. [SPEAKER_00]: You obviously want to consider further work up. [SPEAKER_00]: And echo, for example, you want to remember that [SPEAKER_00]: you may think this is anaphylaxis, but you want to rule out other things like an MI, hence getting a TTE.

[SPEAKER_00]: And then if you have refractory vasodilation and hypotension despite your epinephrine and nor epinephrine, then you can add vasopressin, which can sometimes be helpful. [SPEAKER_00]: As I said, they need to be admitted to the ICU. [SPEAKER_00]: Epinephrine, Epinephrine, is the drug of choice, as I've said.

[SPEAKER_00]: The alpha effect, vasoconstricts, the beta 2 effect bronchodilates, and, interestingly, that beta 2 effect can inhibit further mass cell and base-of-fill de-grandulation. [SPEAKER_00]: This is, again, that use of Epinephrine super, super highly tested. [SPEAKER_00]: If you suspect anaphylaxis, give epinephrine, even if you're not 100% sure, give that small IV dose 5 to 10 mics.

[SPEAKER_00]: Protamine reaction, so even though this is not often, if it's the pulmonary visor-constrictive effect, reaction of proteamine, it may not be anaphylactic, in the sense that it's not through the IGG antibodies, it's through complement activation and thromboxane release, [SPEAKER_00]: you still want to give epinephrine to counteract the effects.

[SPEAKER_00]: So if they give you a scenario where a prodomine's been given and the patient has a, you know, increase in their pulmonary pressures and they get hypotensive, you're going to want to do one of two things. [SPEAKER_00]: You're either going to want to give epinephrine. [SPEAKER_00]: or go back on bypass.

[SPEAKER_00]: So re-hepernization and go back on bypass, they can't really give you both of those options as answer choices. [SPEAKER_00]: Because if they say which of the following is the best choice, give up an effort as one choice and re-hepernize and go back on bypass is another, those are both right.

[SPEAKER_00]: So I think you'll see one or the other, but not both as answer choices. [SPEAKER_00]: and either one would be right, whichever one they list. [SPEAKER_00]: So if you have a massively bad reaction, in other words, you give pro to mean whether it's the full amount or just the testos, and you see total right heart failure.

[SPEAKER_00]: So you see your pulmonary pressures go way up, you see your systemic pressures plunge, then you need to give epi, or you need to give happen and go back on bypass. [SPEAKER_00]: anti-histamines, so one key thing to know about anti-histamines is they don't stop the de-grandulation of mass cells and the release of histamine.

[SPEAKER_00]: Beta 2 action of epinephrine can help stop that, but antihistamines do not. [SPEAKER_00]: What they do is they compete with histamine at the receptor sites. [SPEAKER_00]: So H1 antagonism is what you really want. [SPEAKER_00]: H2 is not that important. [SPEAKER_00]: You want H1 antagonism.

[SPEAKER_00]: And you want to know it's not actually stopping the release of histamine for mass cells. [SPEAKER_00]: It's just competing at the receptor site. [SPEAKER_00]: Also, [SPEAKER_00]: If you give the anti-Histamine rapidly, you can get some anti-dopa-manergic effects and hypotension, so you want to be cognizant of looking for that and give it slowly, especially that hypotension can have a role or you can see it in hypovillemic patients.

[SPEAKER_00]: All right, parioperatively, [SPEAKER_00]: If you know a patient has an allergy, you want to be thinking about a few things. [SPEAKER_00]: So allergic drug reactions account for about 6 to 10 percent of all adverse drug reactions. [SPEAKER_00]: About 5 percent of adults in the US may be allergic to at least one drug.

[SPEAKER_00]: Now patients often confuse any adverse reaction that are not allergic with an allergy. [SPEAKER_00]: So for example someone who gets nauseous and throws up when they get opiates say, oh, I'm allergic to opiates, well, that's not the case. [SPEAKER_00]: That's not a true allergy. [SPEAKER_00]: from an opiate.

[SPEAKER_00]: So that's important to keep in mind as well. [SPEAKER_00]: The mechanism, so drugs, as I said, can produce any one of the four hypersensitivity reactions. [SPEAKER_00]: The most common drug to produce an allergic reaction introoperably are muscle relaxants. [SPEAKER_00]: And people get confused about this because a lot of people have in their minds that it's antibiotics, but it's actually not.

[SPEAKER_00]: It's muscle relaxants. [SPEAKER_00]: And that's true for both succional calling and non-depolarizers. [SPEAKER_00]: They actually share that. [SPEAKER_00]: So don't get thrown off by whether they list sucks, or they list a non-depolarizer as a potential option. [SPEAKER_00]: In terms of evaluation, the most common thing is we're going to just kind of say, look, what was temporally related to this reaction.

[SPEAKER_00]: What did we give before this happened? [SPEAKER_00]: Unfortunately, obviously, we may give a bunch of things in anesthesia and then notice an anaphylactic reaction. [SPEAKER_00]: So we want to keep that in mind. [SPEAKER_00]: There is in the Lisa test, which can identify IGG antibodies against specific things like prodomine.

[SPEAKER_00]: The most common thing to do is enter thermal skin testing after an anaphylactic reaction. [SPEAKER_00]: Now, [SPEAKER_00]: don't get thrown off on test questions because they may say, oh, what's the most important thing to do after an antifelactic reaction immediately after, and they may say, do get skin testing, you might think, oh, maybe I should do that because, you know, I want to figure this out, but that is absolutely not right.

[SPEAKER_00]: You want to stabilize the patient, keep them in the hospital and observe them for those 24 hours, get them stabilized, make sure everything's okay. [SPEAKER_00]: The skin testing, the allergy testing can happen as an outpatient later in the meantime, [SPEAKER_00]: and be very careful of that.

[SPEAKER_00]: So the immediate thing to do is stabilization not skin testing right away, but they will eventually want skin testing to try to identify what they may be allergic to. [SPEAKER_00]: Another thing you may hear about our trip tastes level, so after if you suspect someone is having an allergic reaction, you can draw a test-for trip taste, and if that's particularly elevated, it's suggestive that in fact it may have been a true allergic reaction, but that's often not done in time because we're dealing with stabilizing a patient, which of course is what we should be doing.

[SPEAKER_00]: As I said, the most common agent neuromuscular blocking drugs. [SPEAKER_00]: So those are the most common followed by latex and then antibiotics. [SPEAKER_00]: Neuromuscular blocking agent, the structure is divalent, which means it can cross-link two IgEs really easily without having to bind to a separate carrier molecule.

[SPEAKER_00]: And so that's part of why these are so high risk for this, or at least the most common. [SPEAKER_00]: The problem [SPEAKER_00]: with neuromuscular blocking agents is that they all have cross-reactivity. [SPEAKER_00]: So if someone had an allergic reaction to one of them, you really can't give any until they've had specific skin testing to figure out which one may be safe for them.

[SPEAKER_00]: Most of relaxants can cause histamine release in the absence of an allergic reaction as we've already discussed in Atracurium is the most risky for this, especially at bolus intubating doses. [SPEAKER_00]: You'll hear a lot these days about kind of penicillin allergy and whether patients really have them.

[SPEAKER_00]: So 85% of patients with a history of penicillin allergy are either no longer allergic or never were. [SPEAKER_00]: In terms of cross-reactivity to cephalosporins, it was once thought to be reasonably high, like 10%, but now we know that it's much, much lower, even between different cephalosporins, it's very low.

[SPEAKER_00]: So it's probably safe now you want to check with your own hospital and figure out your own protocol in general if a patient had what we do is if a patient has a history of an anaphylactic reaction to penicillin then we don't want to give a cephalosporin unless we've got testing. [SPEAKER_00]: to make sure they're okay with it or if they've had it and not had a reaction.

[SPEAKER_00]: But for other reactions, things like just a rash, if it's been since childhood, which is very common, someone has a penicillin allergy as a child, then it's now 50 years later. [SPEAKER_00]: They've never had any penicillin since that, if it was just a mild reaction, is almost definitely safe, and we will go ahead and give it because of the advantage of being able [SPEAKER_00]: Local anesthetics are pretty safe, although, of course, like anything you can be allergic to them.

[SPEAKER_00]: But one little tricky thing about local anesthetics is, especially, for example, if a proceduralist is giving some local anesthetic, they often have epinephrine in it. [SPEAKER_00]: And so, if you see a scenario where, you know, a proceduralist or a surgeon is giving some local anesthetic, and then the patient gets tackle cardiac, they get some flushing, some lightheadedness, [SPEAKER_00]: And the question is, is that an anaphylactic reaction or an allergic reaction?

[SPEAKER_00]: It's much more likely, actually, that it's just the epinephrine getting intravascular than it is a true allergy because that's going to happen much more commonly. [SPEAKER_00]: So be aware of that if you see that tested. [SPEAKER_00]: Similarly, be careful of allergy as a distractor answer choice.

[SPEAKER_00]: So often you'll have, you know, you're four or five different answer choices, and they'll throw in there. [SPEAKER_00]: Oh, it's an allergic reaction. [SPEAKER_00]: So I'll give you some examples. [SPEAKER_00]: Remember that Broncospasm can be caused sure by an antifelractive reaction, but also by asthma.

[SPEAKER_00]: So if they tell you about an asthma, it gets light at the end of a case and starts to have weasing, [SPEAKER_00]: and increased airway pressures, and one of the answer choices is anaphylactic reaction it's probably not, especially if one of the other answer choices is just asthma exacerbation.

[SPEAKER_00]: Pulmonary edema can be easy to confuse with bronchospasm as well, so you may hear that not all that weasers is bronchospasm, people with pulmonary edema can have weasings as well, so pay attention to the clinical scenario, a patient who has luringospasm and then develops [SPEAKER_00]: is more likely to have negative pressure pulmonary edema than anaphylaxis.

[SPEAKER_00]: So you can't just think, oh, here's a patient that they're telling me that they have increased peak pressures and they've got weasing, oh, that must be bronchospasm, it must be anaphylaxis. [SPEAKER_00]: No, if a scenario is such that they're leaning you, they've told you they've had luringospasm and now this is happening, it's probably negative pressure pulmonary edema.

[SPEAKER_00]: If they've told you they have asthma and now they're getting light on anesthesia, it's probably bronchospasm from their asthma. [SPEAKER_00]: So don't just pick animal access or analogy as a distractor response. [SPEAKER_00]: Latex is another thing that comes up a lot. [SPEAKER_00]: Natural rubber is what latex is.

[SPEAKER_00]: It causes a type one, IGE dependent hypersensitivity reaction. [SPEAKER_00]: So again, animal active reaction. [SPEAKER_00]: Healthcare workers, kids with spina bifida, [SPEAKER_00]: people with Eurogenital abnormalities, people with ATP, or certain food allergies, interestingly bananas, avocados, and kiwis are the foods that tend to be high risk.

[SPEAKER_00]: These people, all these people I just listed, are at higher risk for a latex allergy. [SPEAKER_00]: Anyone who use suspect has a latex reaction, just like any other anaphylactic reaction, they need to be stabilized. [SPEAKER_00]: They need to be watched, and then they should be referred to an allergist.

[SPEAKER_00]: So again, make sure that you first are stabilizing them. [SPEAKER_00]: You don't want to fall for that distractor of, oh, I need to send them immediately for skin testing. [SPEAKER_00]: Again, we're just going to treat them like they're allergic to latex, and that means it's not urgent for them to get tested, but they do want them to get worked up for that.

[SPEAKER_00]: In the meantime, no, this could be a very serious reaction, and you want to make sure you are stabilizing them. [SPEAKER_00]: Let us know what you thought, go to the website acrack.com where you can leave a comment. [SPEAKER_00]: Others can learn from what you have to say. [SPEAKER_00]: If you are a fan of the show, you can follow us.

[SPEAKER_00]: We're on Twitter, we are on Facebook, we are on Reddit, and we are on Instagram. [SPEAKER_00]: I'm AdJ Wolpa on Twitter, and we're at Acrack Podcast, and you can find us on all those other platforms as well. [SPEAKER_00]: If you are a fan of the show, please consider going to Apple Podcasts or wherever you get your podcasts and leaving a comment and a rating, it really helps others find the show.

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[SPEAKER_00]: You can also make donations anytime by going to paypal.me-slash-acrack, or looking up J.Wallpa on Venmo. [SPEAKER_00]: Thank you so much to those who have already made donations and become patrons, we really appreciate it. [SPEAKER_00]: Thanks as always to our fantastic acrack crew. [SPEAKER_00]: So, Nya Aminat is our tech lead, Chitama Econty, Rachel Furman, and Mohamed Selab are our production assistants and social media managers.

[SPEAKER_00]: Thanks so much for all you do. [SPEAKER_00]: Our original ACRAG Music is by Dr. Dennis Quow. [SPEAKER_00]: You can check out his website at studymusicproject.com. [SPEAKER_00]: All right, that is it for today. [SPEAKER_00]: For the ACRAG podcast, I'm Jed Wolpa. [SPEAKER_00]: Thanks for listening.

[SPEAKER_00]: Remember what you're doing out there every day is really important and valued. [UNKNOWN]: Thank you for watching.

Episode 344: Allergic Response

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