It's hard to really understand the situation you described without some more background. But yes, some horses will fight off the tranqs. I saw that recently with a horse when we were cleaning an ear wound (all cartilage minimal pain) it wasn't even that bad but we were having so much trouble handling him drugged and twitched we got the vet out to do a thorough hopefully one time cleaning. Drugged, drugged some more, AND twitched, he was throwing us around. It wasn't pain as I said it was we were DOING SOMETHING!!!! To him... Sigh. That horse is a drama queen to the max lol.
If you are going to tranq a horse, it has to be before horse gets upset. Trying to do it after horse is ticked off, is worthless.
Better to go in with horse in Happy Happy Happy mode...drugs work better then.