I did play like that until chapter 3. I could actually feel the carpal tunnel syndrome creeping up after about 15 minutes or so.
After a couple hours, I had to start using my pinky, ring finger AND middle finger for shift. Three days in I felt like I might have to amputate my left hand. My wrist was dying from having to bend funny, and my pinky had officially resigned from making any kind of lateral movement whatsoever.
Key binding changes are a must.
I play with my pinky on shift and with my thumb on space, and for a while there I felt like I was getting carpal tunnel syndrome too, but then it stopped hurting. Don't know what happened, maybe my wrist got stronger or something.