Make sure you have an ergonomic setup. Your elbows should be at a right angle; so should your knees. Take frequent breaks, and I agree- if you find your ears to your shoulders, relax, take a deep breath, start again.
Make sure your quilt is supported well, that will make less weight you have to pull around. I keep an outfeed table (just a card table) behind my machine and also to the left side. Sometimes, I add my ironing board to extend the surface- the whole quilt should be supported, not hanging.