I started the game on Impossible mode last night. Died 7 times so far, and I'm sticking with one gun, but God damn it, these bosses take a shitton of damage. The giant necromorph with indestructible carapace took so many hits, I ran out of ammo by the time I was through with it.
I also managed to unlock the "Don't Get Cocky, Kid" trophy...that was a bitch. Keeping the shield damage above 50% isn't easy.