Why are you asking them to click the “Next” button within the tooltip? Ideally, click the “Save” button takes them to the next step in your guide.  

“Additionally, users may not have made any changes, so I can’t force them to click ‘Save”

They may not make any changes, therefore they may not have to click save, if they had to click save then that would be fine and the best solution. 

@scampbell having both the functions of next and click in one tool tip would break the guide.

If you have users to click on save, you can try using click on target element in navigation of guide, which will continue even after the page refreshes as PX expects that after the click the page reloads and guide would continue on new page.

One other way to handle these scenarios in a guide would be to make a quick gif to explain the process.