When my daughter was just in the hospital, they would do her nebs when she was sleeping. They said that is fine. She had Tobi while in the hospital. She does not need her mouth open, they would even do it with her pacifier in her mouth. I would not try to make it any worse than it already is for her. My opinion...I can't imagine putting a nose plug on my daughter! She would freak! (unless it was completely medically necessary, but from my experience I have been told this is not a problem.) Hope this helps!