With RME drivers v4.22 the RME TotalMix application is installed with outputs 1 and 2 assigned to Main Output at -10. To fix this launch the Total Mix application from the taskbar (show hidden icons on lower right). At the bottom right of the application click the Assign button to the right of the Main Output fader and set the Main Out to None. Outputs 1/2 will appear in the left side of the bottom Hardware Output row. Double click on the fader numeric value to bring up the dialog box and set to 0. Make sure that the Outputs 1/2 on the 2nd middle labelled Software Playback is also set to 0 when 1/2 is selected on the Hardware Playback bottom row. If not double click on the fader numeric value to bring up the dialog box and set to 0.
This needs to be done on the 2nd MADI card as well. You can switch between MADI 1 and 2 in the top right drop down.
In the Total Mix menu bar file/save snapshot to save a snapshot to the desktop that can be used to restore the application in case it is ever changed.