Reviving this, because I just found out that you can have the hotkey act as a dedicated pausekey if in Retroarch you assign it to the same button press.
In my situation, my middle front button on my arcade is mapped to keyboard "o".
In Retroarch I assigned both my hotkey and my toggle pause key to "o", and this means that games pauses when I press it, but it still serves as a hotkey, so the other hotkey commands works as well (though the game pauses).
Not sure if this will work as an exit button (the game will then exit when you hotkey), but with pause it does!