Next in our series, premedication for prevention of vaccine reactions.
TLDR: There’s no proven premedication strategy that reliably prevents vaccine adverse events. Focus on risk assessment, appropriate vaccine selection, close monitoring, and prompt treatment if an adverse event occurs.
A more detailed explanation….
Vaccine adverse events (AEs) are uncommon but uncommon doesn’t mean inconsequential. They can range from very mild (like how you might feel crappy after your flu shot) to life-threatening anaphylaxis.
Sometimes, there’s concern because the animal has had an AE in the past. Sometimes, there’s no history of a problem but the owner is still concerned. Regardless, there’s often an attempt to pre-medicate the animal in an attempt to reduce the risk of an AE. Let’s break down the reasons and potential impact.
Various types of AEs can occur and these can be driven by different mechanisms. That’s important for both treatment and prevention.
I’ll save a detailed description of vaccine reaction types for another post, but in broad terms, we can bin them into a few types.
- Inflammatory reactions: This includes local pain and swelling, and systemic signs like fever and malaise. These are essentially exuberant ‘normal’ responses to a vaccine. They are typically mild and self-limiting, but as you may know from your own vaccines, you can sometimes feel pretty rough the day after.
- Anaphylaxis: This is the most sudden, dramatic and life-threatening reaction. It’s a rapid onset immune mediated reaction driven by IgE, which leads to profound mast cell and basophil degranulation, releasing massive amounts of histamine.
- Localized or non-anaphylactic allergic reactions: These are quite rare but are allergic reactions that develop minutes to hours after vaccination. They are likely a response to non-target antigen components on the vaccine (e.g. trace components, stabilizers), not the actual vaccine antigen.
- Immune mediated inflammatory reactions: There are a few types of these, with onset occurring several hours to days after vaccination. These can be of varying severity, from little nodules at the site of injection to severe systemic consequences of immune complex formation.
That’s a pretty crude description of some complex events, but hopefully it sets the scene so we can think about what is typically used to try to prevent AEs.
NSAIDs
Anti-inflammatories are the main approach to treating reactions that result in inflammation and pain. If you have pain, malaise or fever after a flu shot, you’ll probably take ibuprofen. It’s the same general idea for dogs and cats….if they feel rough after vaccination, we can give them an appropriate NSAID. However, that’s in response to a problem, not prophylaxis. CDC says “The prophylactic use of antipyretics (e.g., acetaminophen and ibuprofen) before or at the time of vaccination is not recommended. There is no evidence these will decrease the pain associated with an injection. In addition, some studies have suggested these medications might suppress the immune response to some vaccine antigens.”
Antihistamines
These address histamine-based reactions that are causing issues like hives (if it’s anaphylaxis, we need epinephrine). In dogs and cats, diphenhydramine (Benadryl) is most often used. Yet, there are various issues. Oral absorption (bioavailability) is poor and unpredictable in dogs, and the half life is short. Therefore, it’s effects can be unpredictable, potentially limited and short term. None of those are good properties and something with a limited and short term effect is particularly bad for prophylaxis (if you give it in advance, a lot is gone by the time a reaction starts). Its short half-life also increases the risk of rebound signs if histamine release persists after drug concentrations fall. Intravenous diphenhydramine is useful for treatment of severe reactions as an initial short term treatment for serious cases. Cetirizine is a better oral antihistamine since it’s more potent, has better bioavailability and lasts longer.
But, regardless, these are for treatment, not prevention. In humans, they specifically recommend against pre-treating with antihistamines. One reason is that there’s no evidence that they work. Another is that there’s the potential that if they work to some degree, they might mask the early warning signs of a severe reaction, resulting in delayed recognition. CDC’s guidance around COVID vaccination addresses this the clearest: “Administration of antihistamines to COVID-19 vaccine recipients prior to vaccination to prevent allergic reactions is not recommended. Antihistamines do not prevent anaphylaxis, and their prophylactic use may mask cutaneous symptoms, which could lead to a delay in the diagnosis and management of anaphylaxis.”
Corticosteroids
These drugs have potent anti-inflammatory effects and at higher doses suppress the immune system. They are a core component of treatment of immune-mediated diseases. However, whether at anti-inflammatory or immunosuppressive doses, they can cause a variety of potential severe adverse effects. We’re not going to prevent an immune-mediated reaction with anti-inflammatory doses and it makes no sense to give immunosuppressive doses prior to a vaccine (that aims to produce a good immune response). They are critical for treatment. They have no role in prevention and have a very realistic chance of causing more harm than good prophylactically.
Epinephrine
We need this to treat anaphylaxis but there’s no role in prevention. It’s a short term treatment of imminently threatening, active anaphylaxis.
Anti-nausea medications (e.g. maropitant)
This anti-nausea medication is sometimes used, particularly in cats and there’s no real downside. If the animal was going to get nauseous in response to a vaccine, it might help, if it is given shortly before vaccination. Is nausea likely enough to make it worthwhile? Probably not unless the animal has a known history of repeated nausea events after vaccination. There’s no real downside, though.
So, what can we do to reduce the impact of vaccine AEs?
I focus on two things…assessing vaccination needs and being ready to treat AEs.
We have standard approaches to vaccination that are meant to cover the general population and that usually err on the side of more vaccination. If an animal has a true increased risk of an AE, the cost:benefit calculus changes…the potential risks of vaccination increase and if the value of the vaccine is low, it might be worth skipping the vaccine. In some situations (e.g. DAPP in a dog that has gotten a dose at 16+ weeks of age) I’m happy stopping. In other (e.g. leptospirosis), the value of vaccination is higher so I’ll push it more. Consideration of the risks, benefits and owner’s preferences are key aspects since there’s no one-size-fits-all approach.
Beyond that, I focus on treatment of AEs, not prevention. If they look like they are feeling a bit rough after vaccination, an NSAID is reasonable. If they have what looks like a true histamine-based reaction (e.g. hives), an antihistamine is indicated. I’d start with injectable diphenhydramine for a quick effect and then use oral cetirizine for a more reliable and prolonged effect (compared to oral diphenhydramine).
If it’s a rare immune-mediated disease, then we need immunosuppressive doses of steroids…necessary for immune-mediated disease but not something we want to do unless we have to because of potential complications.
If there’s any hint that anaphylaxis might be present, they get epinephrine.
The greater the concern about the risk of an AE and the greater the risk of a severe AE, the closer I want them monitored. That might mean vaccinating them in the morning and keeping them under close observation in the clinic during the day or ensuring that they are at home with someone to observe them. If there’s thought to be a really high risk of anaphylaxis (but enough of a need for the vaccine to go ahead), the approach might include having an IV catheter in place and having an epinephrine dose readily available, along with close observation and a review of what we’d do if the animal crashes after the vaccine.
Another question that comes up is about splitting vaccines. I’ve covered that before and will rehash it soon for another part of this series, but splitting vaccines doesn’t likely help.
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