I've had this happen, and I think it's a bug in Pyramix, so perhaps this discussion is off topic for this forum.

Sometimes going to the "Configure" page in the Pyramix mixer and then back will force a mixer rebuild which will clear this condition, other times, you have to restart the program. In the cases where this has happened to me, it's been when I have taxed the processor with a some hungry plug-ins. Thankfully, I've been able to save my session before restarting the program. Pyramix version 7 is much better with its VST plugin handling, as I'm seeing much lower CPU load statistics.

Something else to watch out for is a random crash while recording - seemingly out of the blue - where the Pyramix audio output will suddenly get stuck in a loop (I think the loop is the same length as the Fireface's buffer setting, so maybe this brings things back on topic). The only way out of this is a hard re-boot. It's happened to me twice in session - very embarrassing - but thankfully my SPDIF connected backup recorder was able to continue recording without interruption. Apparently the Fireface will continue to output a signal routed directly from the Mic/Line inputs to the SPDIF output (in TotalMix) even though it's outputting the looping audio through the conventional Monitoring channels. This suggests even more strongly that it's a Pyramix issue, so perhaps this discussion is off topic after all. Sorry about that.

Windows XP Pro 32 bit, SP3 on a late 2007 MacBook Pro (version 3.1) running Bootcamp 2.1. Fireface driver 2.9992; Fireface firmware 2.77.