This is a tough one. It could go very smoothly, but it could be a nightmare, you just can't tell with kids. I'm sure you know better than anyone what does\doesn't work with your kids. My thinking is to get to airport earlier enough so he can run around and wear himself out
just enough so he'll be calm for most to of trip, but even that approach may only be part of the solution.
I don't travel a a lot, but I personally feel other passengers need come prepared to have an unhappy baby near by, and have their own personal solutions to help reduce their own stress level. I found a
good headset with a iPod works very well. Unless a crying baby is sitting in the seat next to me, I hardly hear the baby if at all. I know this doesn't help you because you can't bring 100 iPods with you.
You'll need to do what you need to do, but keep in mind that giving kids knock out drugs can be a slippery slope and should only be used in very limited circumstances. I think plane trips qualify.
