I think this is a question for the Nisus people themselves. They very often have clever workarounds. 
I have written a one million signs book as a single document, with footnotes, and nothing ever went wrong, even though in the end I was a bit worried. But of course I had no right-left sections, and only a couple of illustrations.
My two groats of wisdom: is it really Nisus, or isn't maybe your computer is at its limits? For instance because you have too many different programs open? I seem to remember I had such a problem once.
Good luck!
Anne