I highly recommend the sedative
. We travel with an 80 lb dog and two cats twice a year between TV and MA. When I take the the kitties to the vet occasionally they do make a racket, I cannot imagine that chorus for 12 hours.
Before we start the journey to TV, my wife gives them the sedative from the vet. The ride sounds like this:
MEOW, MEOW, meow, meow, meeeeoooooow, meeeee, zzzzzzzzzzzzzzz
We do not let them loose, years ago we took a wire dog crate for medium sized dogs, removed one side and replaced that side with a piece of peg board. I cut out two holes in the peg board the size of the opening in their cat carriers. I attach the carriers to the peg board, put a litter box in the dog crate and the cats have a small two bedroom one bath condo for the trip.