Management of Antivenom-related Allergic reactions

[Sico]

Someone recently emailed me this journal article after my recent snakebite. Some researchers in Sri Lanka conducted an extensive double blind trial over several years, to see whether or not pre-medicating patients with the drugs we commonly use to manage acute allergic reactions (Adrenaline, Hydrocortisone and Promethazine) actually did have a significant effect in the severity of the allergic reaction that the patient experienced.
According to their research roughly 75% of all the patients recieveing AV experienced some form of allergic reaction. Apparently this is common to horse-based serums.
They found that pre-medicating patients with hydrocortisone and promethazinedid NOT significantly help prevent the formation of allergic reactions when AV was administered, pre-medicating with adrenaline 0.25mg SC DID significantly help in limiting the severity of the allergic reaction. Interestingly, pre-medicating with hydrocortisone seemed to somewhat negate the effect of the adrenaline given when an allergic reaction appeared later and adrenaline was administered as part of the treatment.
From my own experience, I did get promethazine and hydrocortisone prior to receiving antivenom, and I still developed a reasonably severe allergic reaction. I did not get adrenaline, although it was drawn up and ready and lying on the table next to me. Obviously I'm not in a hurry to repeat the experience and try a slightly different drug regime to see what works better!
The conclusion of the research is that before you give patients AV, expecting that the majority will develop some form of allergic reaction (whether it be mild, moderate or full blown anaphylactoid/anaphylactic (if it's not the 1st time they are getting AV), pre-dosing the patient with 0.25mg adrenaline 1:1000 SC, will significantly limit the allergic response, and then should a response still occur, the treatment should be as normal where 0.5mg Adrenaline 1:1000 SC is administered along with Promethazine 25mg (IM/IV) and Hydrocortisone (100-500mg IV).
Remember that adrenaline is NEVER under any circumstances given IV to any patient who is conscious.
You can read the whole Journal article here
http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000435

[snake kid]

I don't understand all the big words but I must say very interesting.

[Jen]

Thanks for sharing this Sico. I read it a little while back and I was very surprised by the results. Seeing as though hydrocortisone & antihistamine along with adrenalin is the standard treatment in the case of allergy / anaphylaxis, one would think that the earlier it is administered, the better the outcome. I really found it interesting that there was no positive effect at all of giving steroids early and that in fact the outcome was worse when they were used as a preventative measure.

[toxinologist]

Think about it Jen ... hydrocortisone is not a rapid-acting drug, so why would it be of any benefit whatsoever against an early adverse event occurring soon after antivenom administration? As to the finding in this paper that the use of hydrocortisone was associated with poorer outcomes - this may have been what was observed, but clinically it makes no (causal) sense, and is likely an outcome-unassociated observation. There have already been a number of studies that have shown both corticosteroids and antihistamines to be non-protective against early adverse events due to antivenom administration, so that finding is nothing new. Likewise adrenaline has previously been reported in the literature to be associated with lower rates of early adverse events (including in one of my own papers), so this study is not unique, although it is the largest sample size to date.
Cheers

David

[Jen]

Thanks for the reply David. Seeing as though hydrocort takes 6 hours to kick in I wouldn't expect an improvement immediately, but I was surprised that there seemed to be was a worse outcome in the steroid group. But as you've pointed out it is most likely an outcome-unassociated observation seeings as though it doesn't make sense. Please provide the reference for your paper - I'd be interested in reading it. Thanks

[Sico]

Hi Jen

unrelated to the original post, Hydrocortisone in fact does work a lot faster then generally conceived, although its peak effect is around 5-6 hours. Being an asthmatic and having given myself hydrocortisone IV on occasion when normal Beta2 agonists and Iprotropium haven't been effective, I have noted an onset of effects from the hydrocortisone within 20 minutes from time of administration.
Mark

[toxinologist]

Hi Jen,
The reference is: WILLIAMS DJ, JENSEN S.D., NIMORAKIOTAKIS B., MULLER R., WINKEL, K.D. 2007. Antivenom use, premedication and early adverse reactions in the management of snakebites in rural Papua New Guinea. Toxicon. 49:780-792.
Cheers
David